CA1247097A - Insecticidally active esters of pyrimidinylcyclopropanecarboxylic acids - Google Patents
Insecticidally active esters of pyrimidinylcyclopropanecarboxylic acidsInfo
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- CA1247097A CA1247097A CA000477446A CA477446A CA1247097A CA 1247097 A CA1247097 A CA 1247097A CA 000477446 A CA000477446 A CA 000477446A CA 477446 A CA477446 A CA 477446A CA 1247097 A CA1247097 A CA 1247097A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/26—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N53/00—Biocides, pest repellants or attractants, or plant growth regulators containing cyclopropane carboxylic acids or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/30—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Dentistry (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Agronomy & Crop Science (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
ABSTRACT
Insecticidally Active Esters of Pyrimidinylcyclopropanecarboxylic Acids Novel compounds are provided of formula I wherein :
R2 represents a? ?-branched alkyl group and R represents hydroxy halo or alkyl, useful as intermediates for the preparation of insecticidal compounds of formula I where R
represents the residue of an alcohol, the ester of which with crysenthemic acid, permethrin acid or cyhalothrin acid has insecticidal properties.
Insecticidally Active Esters of Pyrimidinylcyclopropanecarboxylic Acids Novel compounds are provided of formula I wherein :
R2 represents a? ?-branched alkyl group and R represents hydroxy halo or alkyl, useful as intermediates for the preparation of insecticidal compounds of formula I where R
represents the residue of an alcohol, the ester of which with crysenthemic acid, permethrin acid or cyhalothrin acid has insecticidal properties.
Description
~L2~g~
Insecticidally Active Esters of Pyrimidinylcyclopropanecarboxylic ~cids This invention relates to novel cyclopropane acids and derivatives thereo use~ul as intermediates, and to insecticidally active esters of these acids and compositions comprising them. The invention also relates to processes for preparing the novel acids and derivatin~
and to novel compounds useful in such process~s.
In a first aspect this invention provides novel cyclopropane compounds o~ formula I:
R- C -C\ - CH ~ \~ R2 C N (I) , C~13 C~13 wllerein R2 represents an ~-branched alkyl gro~lp, ~referably containillcJ rom 3 to 6 carbon atoms , and either ~a) R
represents hytlroxy, halo (especlally chloro) or alkoxy o up to G carbon atoms, wherein such compounds are useful as intermedia~es Eor in.secticldes, or (b) R represents the group -ORl where ~l is the resid~le oE an alco'nol of ~ormula lS RlOE1 which ~orms an insecticidal ester when combined with chrysanthemic acid or permethrin acid or cyhalothrin acid.
Permethrin acid is 3-(2,2-dichlorovinyl)-2,2 dimethylcyclo-propane carboxylic acid and cyha].othrin acid is 3-(2-chloro-3,3,3-trifluoroprop-l-en-l-yl)-2,2-dimethylcyclo-propane carboxylic acid.
More particularly R represents a group of the following general formula:
(~5)n n4 ~x ~
wherein X i9 oxygen; sulphur, vinylene or a grou~ o~ ~ormula -CR5=Y- where Y is nit~ogen or CR5, R~ is hydrogen, methyl, cyano or ethynyl, each R5 is selected ~rom hydrogen, halogen, and alkyl of up to 4 carbon atoms optionally substituted with halogen, and R6 is hydrogen, halogen, alkyl of up to 4 carbon atom~s, alkenyl of up to 6 carbon atoms, phenyl, ~henoxy or benzyl, or phenyl, phenoxy or benzyl subst;tuted with halo~en or alkyl provided that R6 is hydrogen, halogcn, alkyl or alkenyl, R4 may not represent methyl, cyano or ethynyl.
It will be appreciated that the com~ounds of ~ormula I
are capable of existin~ in difEerent isomeric forms and as mi~tures oE isomers. ~`hus there are clS and trans iso~ers ~rising rotn ~h~ substitution pattern on the cyclo~ropane group and optical isomerism arises Erom the presence o~ the two cl~iral centres in the cyclopropane grou2 leadin~ to the possibility o (~ cls, (-)-cis, (~)-trans and (-)-trans .isomers. Further i~ome~ism may be present in the insecticidally active esters o f the invention if the alcohol moiety contains an alkenyl group or one or ~ore chiral centres. ~ll such in~ividual isomeric forms an~l mixtures thereoE, including racemates, a~e within the scoDe of the invention.
Speci'ic compounds accordins to ormu1a 1 Jseful as intermediates ~here~r P~ represents an alkoxy qroup of up to 6 carbon atoms nclude the methyl, ethyl, propyl and hutyl esters of ~he acids of formula I wherein R2 is one of prop-2-yl, but-2-yl, pent-2-yl, pent-3-yl, 2-met~ylprop-2-yl, 2-methylbut-2-yl, cyclopropyl, and cyclollexyl.
Particularly preferred compounds include :
etnyl (+)-t.rans-2,2-dimethyl-3-(2-prop-2-ylpyrimidin-5-yl)-cyclopropane carboxylate, ethyl (+)-trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)-pyrimidin-5-yl]-cyclopropane carboxylate, and the corresponcling met-nyl and 2-methylprop-2-yl-esters.
The compounds of formula I wherein R is alkoxy of up to 6 carbon atoms may be prepared from the appropriately substituted 5-bromopyrimidine by the following reaction sequence:
(a) A 2 ~-branched alkyl-5-bromopyrimi~.ine is converted to the corresponding 5-formyl derivative by formation of a Grignard product, followed by treatment with dimethylformamide, thus:
N Mg ~I DMF N
R2 ~ ~ Br ~ ~2 ~ gBr , R2~ ~HO
(k) The 5-formylpyrimidine is reacted with an 0,0-dialkyl alkoxycarbonylmethylphosphonate in the ~resence of a base 9uch as sodium hydride to give a 3-(pyrimi~in-5-yl)propenoate, thus:
Insecticidally Active Esters of Pyrimidinylcyclopropanecarboxylic ~cids This invention relates to novel cyclopropane acids and derivatives thereo use~ul as intermediates, and to insecticidally active esters of these acids and compositions comprising them. The invention also relates to processes for preparing the novel acids and derivatin~
and to novel compounds useful in such process~s.
In a first aspect this invention provides novel cyclopropane compounds o~ formula I:
R- C -C\ - CH ~ \~ R2 C N (I) , C~13 C~13 wllerein R2 represents an ~-branched alkyl gro~lp, ~referably containillcJ rom 3 to 6 carbon atoms , and either ~a) R
represents hytlroxy, halo (especlally chloro) or alkoxy o up to G carbon atoms, wherein such compounds are useful as intermedia~es Eor in.secticldes, or (b) R represents the group -ORl where ~l is the resid~le oE an alco'nol of ~ormula lS RlOE1 which ~orms an insecticidal ester when combined with chrysanthemic acid or permethrin acid or cyhalothrin acid.
Permethrin acid is 3-(2,2-dichlorovinyl)-2,2 dimethylcyclo-propane carboxylic acid and cyha].othrin acid is 3-(2-chloro-3,3,3-trifluoroprop-l-en-l-yl)-2,2-dimethylcyclo-propane carboxylic acid.
More particularly R represents a group of the following general formula:
(~5)n n4 ~x ~
wherein X i9 oxygen; sulphur, vinylene or a grou~ o~ ~ormula -CR5=Y- where Y is nit~ogen or CR5, R~ is hydrogen, methyl, cyano or ethynyl, each R5 is selected ~rom hydrogen, halogen, and alkyl of up to 4 carbon atoms optionally substituted with halogen, and R6 is hydrogen, halogen, alkyl of up to 4 carbon atom~s, alkenyl of up to 6 carbon atoms, phenyl, ~henoxy or benzyl, or phenyl, phenoxy or benzyl subst;tuted with halo~en or alkyl provided that R6 is hydrogen, halogcn, alkyl or alkenyl, R4 may not represent methyl, cyano or ethynyl.
It will be appreciated that the com~ounds of ~ormula I
are capable of existin~ in difEerent isomeric forms and as mi~tures oE isomers. ~`hus there are clS and trans iso~ers ~rising rotn ~h~ substitution pattern on the cyclo~ropane group and optical isomerism arises Erom the presence o~ the two cl~iral centres in the cyclopropane grou2 leadin~ to the possibility o (~ cls, (-)-cis, (~)-trans and (-)-trans .isomers. Further i~ome~ism may be present in the insecticidally active esters o f the invention if the alcohol moiety contains an alkenyl group or one or ~ore chiral centres. ~ll such in~ividual isomeric forms an~l mixtures thereoE, including racemates, a~e within the scoDe of the invention.
Speci'ic compounds accordins to ormu1a 1 Jseful as intermediates ~here~r P~ represents an alkoxy qroup of up to 6 carbon atoms nclude the methyl, ethyl, propyl and hutyl esters of ~he acids of formula I wherein R2 is one of prop-2-yl, but-2-yl, pent-2-yl, pent-3-yl, 2-met~ylprop-2-yl, 2-methylbut-2-yl, cyclopropyl, and cyclollexyl.
Particularly preferred compounds include :
etnyl (+)-t.rans-2,2-dimethyl-3-(2-prop-2-ylpyrimidin-5-yl)-cyclopropane carboxylate, ethyl (+)-trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)-pyrimidin-5-yl]-cyclopropane carboxylate, and the corresponcling met-nyl and 2-methylprop-2-yl-esters.
The compounds of formula I wherein R is alkoxy of up to 6 carbon atoms may be prepared from the appropriately substituted 5-bromopyrimidine by the following reaction sequence:
(a) A 2 ~-branched alkyl-5-bromopyrimi~.ine is converted to the corresponding 5-formyl derivative by formation of a Grignard product, followed by treatment with dimethylformamide, thus:
N Mg ~I DMF N
R2 ~ ~ Br ~ ~2 ~ gBr , R2~ ~HO
(k) The 5-formylpyrimidine is reacted with an 0,0-dialkyl alkoxycarbonylmethylphosphonate in the ~resence of a base 9uch as sodium hydride to give a 3-(pyrimi~in-5-yl)propenoate, thus:
2 (Eto)2p(o)cH2co2R9 N-R ~ ~ CHO ~- - - > R -~ ~ CH=CH-CO2R
N NaH N
(c) The pyrimidinylpropenoate is reacted with ~n isopropyl triphenyl phosphonium salt in the presence of an organo metallic reagent such as n-butyllithium to give the cyclopropane ester, thus:
N [ iPr-PPh3 ]~
R2~ ~ CH=C~_C02~9 ~ R2~ 3 c~ CH_C02Rg N n-BuLi ~ C
CI~3 CH3 In an alternative procedure for preparing the 3-pyrimidin-5-yl-propenoates a 5-bromopyrimidine may be reacted directly with an alkyl propenoate (especially 1,1-dimeth~lethyl-propenoate) in the presence of a palladium II
salt (eg. palladium II acetate), tetramethyl ethylene diamine and, preferably, a phosphine derivative (eg.
triphenyl phosphine), thus:
CH2=CFl-C02R /Pd(OAC)2 R2 ~ ~ Br ~ ~ R2 ~/ ~ CH=CH-C02R9 ~I TMED/ph3p N
Some of the 5-bromopyrimidines used as ~tarting materials in this sequence are novel. They can be prepared by reaction o~ a mucobrom.ic acid derivative with an appropriate amidine, followed by decarboxylation of the pyrimidine carboxylic acid thus:
O WH
H-C co2~ R2-C-NH2 ~t C=C R2~t ~ Br Br Br ~t ~
-CO~
~2 ~ ~ Br ~2~ 7 An alternative procedure for preparin~ the compounds of ~'ormula I wherein R is alkoxy of up to 6 carbon atoms, and R2 is a defined hereinabove employs the following reaction sequence:
(a) The ylid obtained by treating a phosphonium salt of formula:
[R70-CH2-P(~8)3~ Y
wherein Y~ i5 any suitable anion, eg. the chloride or bromide ion, and R7 and R8 are alkyl or aryl groups, preferably R7 is alkyl of up to 6 carbon atoms such as methyl or ethyl and R8 is phenyl, with a strong base in an aprotic solvent preferably dimsyl sodium in dimethyl sulphoxide (obtained by reaction of sodium hydride with dimethyl sulphoxide), is reacted with a compound of formula:
O O
Il 11 R- C - CH - CH- C- H
C~3 CH3 to obtain a compound of formula III
1l 7 R -C - ~ -/CH- CH~=CH -OR
/ C (III) (b) The compound of formula III is treated with phosphoryl chloride and dimethylformamide under the conditior.s of the Vilsmeier-Haack reac~ion to obtain a compound of formula TV
and/or a compound of formula V
R-C -CH / H- C = CH -G (IV) G=~R7 C (V~ G=M(CH3)2 ~H3 CH3 (c) Compound ~V and/or compound V is reacted with an amidine o~ formula-M~
R3 -C -~H2 preferably in the presence of a base such as sodium methoxide in methanol to provide the compound of formula I
S wherein R is alkoxy as defined above.
The compounds of formulae III, IV and V have not previously been described. Accordingly a urther aspect the present invention provides compounds of formula III, IV
and V are hereinbeEore defined useful as intermediates for the production o~ compounds o ~ormula I.
Pre~erred compounds o formula III include t~a (~-cls and (~)-trans isomers of the compounds where R is methoxy or ethoxy and R7 is alkyl of up to 6 carbon atoms including the following:
methyl (_)-trans-3-[(E,Z)-2-methoxyvinyl]-2,2-dim~thyl-cyclopropane carboxylate methyl (_)-cis-3-t(E,Z)-2-methoxyvinyl]-2, -dimethylcy-clopropane carboxylate ethyl (_)-trans-3-[(E,Z)-2-methoxyvinyl]-2,2-dimethylcy-clopropane carboxylate ethyl (~)-cls-3-~(E,Z)-2-met'no2yvinyl]-2,2-dimethy-cyclo-propane carboxylate f~ 7~3~g7 The corresponding compounds of formula IV and formula V are also preferred, including the following:
methyl (+)-trans-3-[(E,Z)-l-formyl-2-methoxyvinyl]-2,2-dimethylcyclopropane carboxylate methyl (~)-ClS-3-[ (E,Z)-l-formyl-2-methoxyvinyl~-2,2-dimethylcyclopropane carboxylate methyl (+)-trans-3-r(E,Z)-2-dimethylamino-1-formylvinyl3-2,2-dimethylcyclopropane carboxylate methyl(+)-cls-3-[(E,Z)-2-dimethylamino-1-formylvinyl~-2,2-dimethylcyclopropane carboxylate together with the corresponding ethyl esters.
Further details of all these processes are set forth hereinafter in the Examples. ~he compounds of formula I wherein R represents hydroxy may be obtained by hydrolysis of the alkyl esters, preferably by alkaline hydrolysis using eg. aqueous alcoholic sodium hydroxide, and may be used directly in the synthesis of insecticidally useful esters or may be first converted to the compounds of formula I wherein R represents halo, preferably chloro, by reaction with a suitable halogenating agent such as thionyl chloride. Speciic insec-ticidally useful compounds according to the invention include the esters derived from each of:
4-methyl-2,3,5,~-tetrafluorobenzyl alcohol pentafluorobenzyl alcohol 4-allyl-2,3,5,6-tetrafluorobenzyl alcohol 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol
N NaH N
(c) The pyrimidinylpropenoate is reacted with ~n isopropyl triphenyl phosphonium salt in the presence of an organo metallic reagent such as n-butyllithium to give the cyclopropane ester, thus:
N [ iPr-PPh3 ]~
R2~ ~ CH=C~_C02~9 ~ R2~ 3 c~ CH_C02Rg N n-BuLi ~ C
CI~3 CH3 In an alternative procedure for preparing the 3-pyrimidin-5-yl-propenoates a 5-bromopyrimidine may be reacted directly with an alkyl propenoate (especially 1,1-dimeth~lethyl-propenoate) in the presence of a palladium II
salt (eg. palladium II acetate), tetramethyl ethylene diamine and, preferably, a phosphine derivative (eg.
triphenyl phosphine), thus:
CH2=CFl-C02R /Pd(OAC)2 R2 ~ ~ Br ~ ~ R2 ~/ ~ CH=CH-C02R9 ~I TMED/ph3p N
Some of the 5-bromopyrimidines used as ~tarting materials in this sequence are novel. They can be prepared by reaction o~ a mucobrom.ic acid derivative with an appropriate amidine, followed by decarboxylation of the pyrimidine carboxylic acid thus:
O WH
H-C co2~ R2-C-NH2 ~t C=C R2~t ~ Br Br Br ~t ~
-CO~
~2 ~ ~ Br ~2~ 7 An alternative procedure for preparin~ the compounds of ~'ormula I wherein R is alkoxy of up to 6 carbon atoms, and R2 is a defined hereinabove employs the following reaction sequence:
(a) The ylid obtained by treating a phosphonium salt of formula:
[R70-CH2-P(~8)3~ Y
wherein Y~ i5 any suitable anion, eg. the chloride or bromide ion, and R7 and R8 are alkyl or aryl groups, preferably R7 is alkyl of up to 6 carbon atoms such as methyl or ethyl and R8 is phenyl, with a strong base in an aprotic solvent preferably dimsyl sodium in dimethyl sulphoxide (obtained by reaction of sodium hydride with dimethyl sulphoxide), is reacted with a compound of formula:
O O
Il 11 R- C - CH - CH- C- H
C~3 CH3 to obtain a compound of formula III
1l 7 R -C - ~ -/CH- CH~=CH -OR
/ C (III) (b) The compound of formula III is treated with phosphoryl chloride and dimethylformamide under the conditior.s of the Vilsmeier-Haack reac~ion to obtain a compound of formula TV
and/or a compound of formula V
R-C -CH / H- C = CH -G (IV) G=~R7 C (V~ G=M(CH3)2 ~H3 CH3 (c) Compound ~V and/or compound V is reacted with an amidine o~ formula-M~
R3 -C -~H2 preferably in the presence of a base such as sodium methoxide in methanol to provide the compound of formula I
S wherein R is alkoxy as defined above.
The compounds of formulae III, IV and V have not previously been described. Accordingly a urther aspect the present invention provides compounds of formula III, IV
and V are hereinbeEore defined useful as intermediates for the production o~ compounds o ~ormula I.
Pre~erred compounds o formula III include t~a (~-cls and (~)-trans isomers of the compounds where R is methoxy or ethoxy and R7 is alkyl of up to 6 carbon atoms including the following:
methyl (_)-trans-3-[(E,Z)-2-methoxyvinyl]-2,2-dim~thyl-cyclopropane carboxylate methyl (_)-cis-3-t(E,Z)-2-methoxyvinyl]-2, -dimethylcy-clopropane carboxylate ethyl (_)-trans-3-[(E,Z)-2-methoxyvinyl]-2,2-dimethylcy-clopropane carboxylate ethyl (~)-cls-3-~(E,Z)-2-met'no2yvinyl]-2,2-dimethy-cyclo-propane carboxylate f~ 7~3~g7 The corresponding compounds of formula IV and formula V are also preferred, including the following:
methyl (+)-trans-3-[(E,Z)-l-formyl-2-methoxyvinyl]-2,2-dimethylcyclopropane carboxylate methyl (~)-ClS-3-[ (E,Z)-l-formyl-2-methoxyvinyl~-2,2-dimethylcyclopropane carboxylate methyl (+)-trans-3-r(E,Z)-2-dimethylamino-1-formylvinyl3-2,2-dimethylcyclopropane carboxylate methyl(+)-cls-3-[(E,Z)-2-dimethylamino-1-formylvinyl~-2,2-dimethylcyclopropane carboxylate together with the corresponding ethyl esters.
Further details of all these processes are set forth hereinafter in the Examples. ~he compounds of formula I wherein R represents hydroxy may be obtained by hydrolysis of the alkyl esters, preferably by alkaline hydrolysis using eg. aqueous alcoholic sodium hydroxide, and may be used directly in the synthesis of insecticidally useful esters or may be first converted to the compounds of formula I wherein R represents halo, preferably chloro, by reaction with a suitable halogenating agent such as thionyl chloride. Speciic insec-ticidally useful compounds according to the invention include the esters derived from each of:
4-methyl-2,3,5,~-tetrafluorobenzyl alcohol pentafluorobenzyl alcohol 4-allyl-2,3,5,6-tetrafluorobenzyl alcohol 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol
3-phenoxybenzyl alcohol ~-cyano-3-phenoxybenzyl alcohol 6-phenoxypyrid-2-ylmethanol 1-cyano-1-(6-phenoxypyrid-2-yl)methanol 3-(4-chlorophenoxybenzyl~ alcohol ~-ethynyl-3-phenoxybenzyl alcohols 1-(6-phenoxypyrid-2-yl)ethanol
4-fluoro-3-phenoxybenzyl alcohol ~-cyano-4-fluoro-3-phenoxybenzyl alcohol
5-benzyl-3-furylmethanol 2-allyl-3-methyl-~-hydroxycyclopent-2-enone 2-methyl-3-phenylbenzyl alcohol includiny, where appropriate, slngle isomers and racemates thereof, and each of the acids of formula I (in the rorm of the racemic mixture of the trans isomers), or a single isomer thereo~, wherein R2 is one of prop-2-yl, but~2-yl, pent-2-yl, pent-3-yl, 2-methylprop-2-yl, 2-methylbut-2-yl, cyclopropyl and cyclohexyl.
Particularly preerred compounds include:
4-raethyl-2,3,5,6-tetrafluorobenzyl (+)-trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate (hereinafter "Compound I").
4-allyl-2,3,5,6-tetrafluorobenzyl (+)-trans-2,2-dimethyl-20 3-[2-(2-methylprop-2-yl)pyrimidin-5-yllcyclopropane carboxylate (hereinater '`Compound II").
3-phenoxybenzyl (+)-trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate (hereinafter "Compound III").
25 (~ -cyano-3-phenoxybenzyl (~)-trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl~cyclopropane carboxylate lhereinafter "Compound IV").
Particularly preerred compounds include:
4-raethyl-2,3,5,6-tetrafluorobenzyl (+)-trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate (hereinafter "Compound I").
4-allyl-2,3,5,6-tetrafluorobenzyl (+)-trans-2,2-dimethyl-20 3-[2-(2-methylprop-2-yl)pyrimidin-5-yllcyclopropane carboxylate (hereinater '`Compound II").
3-phenoxybenzyl (+)-trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate (hereinafter "Compound III").
25 (~ -cyano-3-phenoxybenzyl (~)-trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl~cyclopropane carboxylate lhereinafter "Compound IV").
6-phenoxypyrld-2-ylmethyl (+~-trans-2,2-dimethyl-3-[2-~2-methylprop-2-yl)pyrimidin-5-yl]cyclopropane carboxyL?.te (herelnafter "Compound V").
(+)-l-cyano-1-(6-phenoxypyrid-2-yl)methyl (+)-trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)pyrimidin 5-yl]
cyclopropane carboxylate (hareinafter "Compound VI").
2-methyl-3-phenylbenzyl (+)-trans-2,2-dimethyl-3-[2-methyl-prop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate (hereinafter "Compound VII").
4-fluoro-3-phenoxybenzyl (+)-trans-2,2-dimethyl-3-[2-methylprop-2-yl)pyrirnidin-5-yl~cyclopropane carboxylate (hereinafter "Compound VIII").
(+)-1-cyano-1-(6-phenoxypyrid-2-yl)methyl (+)-trans-2,2 dimethyl-3-(2-prop-2-yl-pyrimidin-5-yl)cyclopropane carboxylate (hereinafter "Compound IX").
(+)-l-cyano-1-(6-phenoxypyrid-2-yl)methyl (+)-trans-2,2-dimethyl-3-(2-cyclohexylpyrimidin-5-yl)cyclopropane carboxylate (hereinafter "Compound X").
~ l-cyano-1-(6-phenoxypyrid-2-yl)methyl (+)-trans=2,2-dimethyl-3-(2-cyclopropylpyrimidin-5-yl)cyclopropane carboxylate (hereinafter "Compound XI").
(+)-1-(6-phenoxypyrid-2-yl)ethyl (+)-trans-2,2-dimelhyl-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl)cyclopropane carboxylate (hereinafter "Compound XII").
pentafluorobenzyl (+)-trans-2,2-dimethyl-3-[2-(2-methyl-prop-2-yl)pyrimidin-5-yl~cyclopropane carboxylate (hereinater "Compound XiII").
(+)~X-ethynyl-3-phenoxybenzyl (+)-trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate (hereinafter "Compound XIV").
~2,~
4-methoxymethyl-2,3,5,6-tetrafluorobenzyl (+)-trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl~cyclo-propane carboxylate (hereinafter '`Compound XV").
2 methyl-3-phenylbenzyl (+)-trans-2,2-dimethyl-3-(2-prop-2-ylpyrimidin-5-yl)cyclopropane carboxylate (hereinater "Compound XVI").
The insecticidally active compounds of the invention accordi~g to Formula I are esters and may be prepared by conventional esterification processes, of which the following are examples.
(a) An acid of formula:-O
R2 ~ ~ CH - /CH-~-Q II
C~
where Q represants the hydroxy group and R2 has any of the meanings given hereinabove, may be reacted directly with an alcohol of formula Rl-OH
5III) where Rl has any of the meanings glven hereinabove, the reaction preferably taking place in the presence of an acid catalyst, for exampls, dry hydrogen chloride, or a dehydrating agent, such as for example, dicyclohexyl carbodiimide.
(b) An acid halide of formula II where Q .epresents a halogen atom, preferably a chlorine atom, and R2 has any of the meanings yiven hereinabove, may bs reacted with an alcohol of formula III, the reaction p eferzbly taking place in the presence of a base, for example, pyridine, alXali metal hydroxide or carbonate, or al~ali metal alkoxlde.
(c) An acid of formula II where Q represents the hydroxy group or, preferably, an alkali metal salt thereo, may be reacted with halide of formula Ql-Rl (IV) wherein Ql represents a halogen atom, preferably the cnloxine atom, and Rl has any of the meanings given hereinabova, or with the quaternary ammonium salts ~ derived from such halides with tertiary amines, for example pyridine, or trialXyl a~ines such as triethylamine.
(d) A lower alkyl ester of formula (II) where Q represents a lower alkoxy group containing up to six carbon atoms, preferably the methoxy or etho~y group, and R2 has any of the meanings given hereinabove, is heated with an alcohol of formula III to efect a transesterification reaction. Preferably the process is performed in the presence of a suitahle catalyst, for example, an alXali metal al~.oxide, such as sodium metho~ide, or an alkylated titanium derivative, such as tetramethyl titanate.
A'l of these conventional processes for the preparation of esters may be carried out using solvents and diluents for the various reactants where appropriate, ~.Q~
may be accelerated or lead to higher yields of ~roduct w~en performed at elevated temperatures or in the presence of appropriate catalysts, for example phase-transer catalysts.
The preparation of individual isomers may be carried out in the same manner but commencing from the corres-ponding individual isomers of compounds of formula ~I.
T~ese may be obtained by conventional isomer separation techniques from mixtures of isomers. Thus cls and trans isomers rnay be separated by fractional crystallisation of the carboxylic acids or salts thereor, whilst the various optically active species may be obtained by fractional crystallisation of salts of the acids with optically active amines, followed by regeneration of the optically pure acid. The optically pure isomeric form of the acid (or its equi~alent acid chloride or ester) may then be reacted with the appropriate alcohol to produce a compound of formula I
in the form of an individually pure isomer thereof.
The compounds of formula I may be used to combat and control infestations of insect pests and also other invertebrate pests, for example, acarine pests. The insect and acarine pests which may be combatted and controlled by the use of the invention compounds include those pests associated with agriculture (which term 1ncludes the growing of crops for food and fibre products, horticulture 1~ and animal husbandry), forestry, the stora~e of products of vegetable origin, such as fruit, grain and timber, and also those pests associated with the transmission of fliseases of man and animals.
In order to apply the compounds to the locus of the pests they are usually formulated into compositions which include in addition to the insecticidally active ingredient or ingredients of formul.a I suitable inert diluent or carrier materials, and/or surface active agents. The cor.lpositions may also comprise another pesticidal material, for example another insecticide or acaricide, or a fungicide, or may also comprise an insecticide synergist, such as for example dodecyl imidazole, safroxan, or piperonyl butoxide.
The compositions may be in the form of dusting powders wherein the active ingredient is mixed with a solid diluent or carrier, for example Xaolin, bentonite, kieselguhr, or talc, or they may be in the form of granules, wherein tne active ingredient is absorbed in a porous granular m2terial for example pumice.
Al-ternatively the compositions may be in the form of liquid preparations to be used as dips or sprays, whi~h are generally aqueous dispersions or emulsions of the active ingredient i.n the presencQ of one or more Xnown wetting agents, dispersing agents or emulsifying agents (surface active agents).
Uetting agents, dispersing agents and emulsifying agents may ~e of the cationic, anionic or non-ionic typeO
6uitable agents of the cationic type include, for example, quaternary ammonium com c,unds, for example cetyltrimethyl ammonium bromide. Suitable agents of the anionic type include, Eor exa~.ple, soaps, salts of aliphatic monoestars of su].phuric acid, for example sodium lauryl sulphate, salts of sulphonated aromatic compounds, for example sodium dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, or butylnaphthalene sulphonate, and a mixture of the sodium salts of diisopropyl- and triiso-propylnaphthalene ~ulphonates. Suitable agents of the non-ionic type include, ~or example, the condensation products of ethylene oxide with fatty alcohols such as oleyl alcohol or cetyl alcohol, or with alkyl phenols such as octyl phenol, nonyl phenol and octyl cresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, the condensation products of the said partial esters with etllylene oxide, and the lecithins.
Ths compositions may be prepared by dis301ving the active ingredient in a suitable solvent, ror example, a ketonic solvent such as diacetone alcohol, or an aromatic solver,t such as trimethylben~ene and adding the mixture so obtained to water which may cor.tain one or more known wetting, dispersing or emulsifying agents.
Other suitable organic solvenis are dimethyl formam.de, ethylene dichloride, isopropyl alcohol, propyiene glycol and other glycols, diacetone alcohol, toluene, kerosene, ~whlte oil, methylnaphthalene, xylenes and trichloroe~hylene, ~J-methyl-2-pyrrolidone and tetrahydrofurfuryl alcohol (T~FA).
The compositions which are to be used in the form of aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient or ingredients, the said concentrate to be diluted with water before use. These concentrates are often required to withstand storage for prolo~ged periods and after such storage, to be capable of dilution with water to form aqueous preparations which remain homogenous for a sufficient time to enable them to be applied by conventional spray equipment. The concentrates may contain 10-85% by weight of the active ingredient or ingredients. ~1hen diluted to form aqueous preparations such preparations may contain varying amounts of the active ingredient depending upon the purpose for which Lhey are to be used. For agricultural or horticultural purposes, an a~ueous preparation containing between O.OOOl~ and O.l~ by weight O;e the active ingredient is particularly useful.
In use the compositions are applied to the pests, to the locus of the pests, to the habitat of the pests, or to growing plants liable to infestation by the pests, by any of the known means or applying pesticidal compositions, for example, by dustinc~ or spraying.
The compositions of the invention are toxic to a variety of insect and other invertebrate pests, including, for example, the following:
Myzus persicae (aphids) Aphis fabae (aphids) Megoura viceae (aphids) Aedes aegypti (mosquitoes) Dysdercus fasciatus (capsids) Musca domestica (houseflies) Pieris brassicae (white butterfly, larvae) Plutella maculipennis (diamond back moth, larvae) Phaedon cochleariae (mustard beetle) _ Tetranychus cinnabarinus (carmine spider mite) Tetranychus urticae (red spider mites) ~onidiella spp. (scale insects) Trialeuroides spp. (white flies) Blattella germanica (coc~roaches) -Spodoptera littoralis (cotton leaf worm) Heliothis virescens (tobacco budworms) Chortiocetes terminifera (locusts) Diabrotica spp. (rootworms) Agrotis spp. (cutworms) Chilo partellus (mai3e stem borers) The compounds of formula I and compositions comprising them have shown themselves to be particularly useful in controlling acarine pests o~ plants such as red mites and rust mites as well as lepidopteran pests of cotton, for example Spodoptera spp. and Heliothis spp. The compounds may also be used to combat pests which inhabit the soil, for example Diabrotica spp. They ~.ay also be useful in combating insect and acarine E~ests which infest domestic animals, such as Lucilia sericata, and ixodid ticks such as Boophilus 5pp., Ixodes spp., mblyomma spp., Rhipicephalus spp., and Dermaceutor spp. ~ney may be effective in combating both susceptible and resistant strains of these pests in their adult, larval and intermediate sta~es of growth, and may be applied to the infested host an~mal by topical, oral or parenteral administration.
The following Examples illus-trate various aspects o~
this invention. In the preparation Examples the products were usually identified and characterised 'Dy means of nuclear magnetic resonance spectroscopy and infra red spectroscopy. In each case where a product is specifically named its spectral characteristics are consistent with the assigned structure.
EXA~PLE 1 This Example illustrates the preparation of pivalamidine hydrochloride.
A s-tirred mixture of trimethylacetonitrile (43g;
0.51M) and dry ethanol (24g, 0.51M) was cooled using an ice/salt bath whilst dry hydrogen chloride gas was passed into the mixture over a period of 90 minutes, until a total of 21gms had been ta~en up. The mixture was then kept for 2 days at the ambient temperature a ter w~ich it was diluted with dry diethyl ether (500cm3) to precipitate ethyl trimethyl ace-timidate hydrochloride which was collected by filtration (34.5g). To this was added portionwise a solution of dry ammonia gas (6g) in dry ethanol (50cm3) with vigorous stirring. The solid gradually dissolved during the coursa of the addition and the resultant solution was kept at the ambient temperature for 20 hours aEter which t~e solvent was removed by evaporation under reduced pressure and the residual solid washed with diethyl ether to yield pivalamidine hydrochloride (23g).
EX~I~PLE 2 This Example illustrates the preparation of 5-bromo-2-(2-methylprop-2-yl)pyrimidine-4-carboxylic acid.
A solution of sodium ethoxide in ethanol (14.5cm3 o the solution obtained by dissolving sodium (1.38g) in dry ethanol (24cm3)) was added carefully to a stirred mixture of pivalamidine hydrochloride (5.18g) and dry ethanol (5cm3) at 40C. After stirring the mixture for a further 10 minutes a solution of mucobrcmic acid (5.4cm3 of the solution obtained by dissolvir.g mucobromic acid (5.16g) in dry ethanol (3.0cm3)) was added to the mixture resulting in an exothermic reaction during which the temperature rose to 65C. After a period the temperature had reduced to 50C
and the remainder of the sodium ethoxide solution and the remainder of mucobromic acid solution were added. ~he reaction temperature was maintaired at ;0C for 1 hour by external heating, after which the insoluble portion was removed by filtration at that temperature, washed wit'n ethanol and the washings and filtrate combined. After removing the solvent by evaporation under reduced pressure the residual solid was washed with dilute hydrochloric acid (2M, lOcm3), with water and dried to yield S-bromo-2(2-methylpro-2-yl)pyrimidine-4-carboxylic acid (3.8g), melting point 142-144C (with decomposition) ~.m.r and infrared spectra were consistent with this identification.
H ~MR (CDC13) ~ 5 (s,9H); 9.05 (s,lEI); 9.44 (broad s, lH).
lS Infra red (paraffin mull) : 2940, 286G, 2500 (broad), 1710, 1570, 1370, 1305, 1290, 1220, 1190, 1175, 750, 680 cm~
EXAMPL~ 3 This Example illustrates the preparation of 5-bromo-2-(2-methylprop-2-yl)pyrimidine.
5-Bromo-2-(2-methylprop-2-yl)p~rimidine-4-carboxylic acid (l.Og) was heated with stirring at 145C after which the decarboxylated product was obtained by distillation using a Kugelrohr apparatus under water pump pressure. The distillate solidified on cooling to yield 5-bromo-2-(2-methylprop-2-yl)pyrimidine (0.6g) melting point 50-51~C.
N.m.r. and infra-red spectra were consistent with this identification.
1~ nmr (CDC13) ~ : 1.39 (s,9H); 8.71 (s,2E~).
Infra red (paraffin mull) : 2940, 2860, 1530, 14SO, 1420, 1170, 1010, 810, 640 cm-l This ~xample illustrates the preparation of 2-(2-methylprop-2-yl)pyrimidine-5-carboxaldehyde.
A solution of 5-bromo-2-(2-methylprop-2-yl)pyrimidine (7.6g, 0.035M) in dry tetrahydrofuran (SOcm3) was added in small portions to magnesium turnings (0.95g, Grignard grade) in the presence of a few crystals of iodineO Ths rate of addition was controlled by the rate of the exothermic reaction. ~Ihen the additi.on was complete the mixture was warmed to complete the reaction. After cooliny t'he mixture to 5C, a solution of dimethyl formamide (2.58g) in tetrahydrofuran (15ml) was added thereto dropwise. The mixture was allowed to warm to the ambient temperature with stirring ovar a period of 2 hours and ~ept for 16 hours without stirring. After adding water (5cm3) to the mixture the tetrahydrofuran was removed by evaporation under reduced pre~sure and the residue partitioned between dilute aqueous ammonium c'hlorid0 solution (lOOcm3) and diethyl ether (150cm3). The aqueous phase was extracted with ether (150cm3) and t'he extract combined with the ether phase, washed with water, and dried over anhydrous magnesium sulphate. Evaporation of the ether under reduced pressure yielded an oily solid residue ($.8g) which was purified by dry column chromatography using a silica column eluted with a mixture of methylene chloride (100 parts by volume) al1d ethyl acetate (2 parts by volume) to give 2-(2-methylprop-2-yl)pyrimidine-5-carboxaldehyde (3.4g) melting point S2-83C.
Infra red (paraffin mull): 2940, 2860, 1700, 1590, 1430, 1230, 1150, 860, 650 cm~
E~AMPLE 5 This Example illustrates the preparation of ethyl 3-[2-(1,1-dimethylethyl)pyrimidin-5-yl] propenoate.
A solution of 0,0-diethyl ethoxycarbonyl-methylphosphonate (3.93g) in dry diethyl ether (20cm3) was added dropwise to a stirred suspension of sodium hydride (0.54g of a 50% oil dispersion) in dry S diethyl ether (30cm3) at -5C and the mixture stirred thereafter for a further period of 90 minutes. A solution of 2-(2-methylprop-2-yl)pyrimidine-5carboxaldehyde (2.88g) in dry diethy~ ether (40cm3) ~as added dropwise to this stirred mixture at 0C, the resultant mixture allowed to warm to the ambient temperature with stirring over 2 hours after which it was kept at the ambient temperatures for 16 hours. The mixture was partitioned between water (150cm3) and diethyl ether (250cm3), the aqueous phase extracted with ether (2~0cm3) and the extracts combined with the ethereal phase. After washing with water (200cm3) and drying over anhydrous magnesium sulphate, the solvent was evaporated under reduced pressure and residual oil subjected to dry column chromatography using a silica column and, as eluent, dichloromethane containing 5% v/
ethyl acetate, to yield ethyl 3-[2-(2-methylprop-2-yl)pyrimidin-5-yl]propenoate (3.6g) which solidiied on standing, melting point 43-45C. ~T.m.r.
and inra-red spectral data indicate the product as consisting of the trans isomer.
lrA ~MR (CDC13) ~ : 1.35 (t,3H); 1.42 (s,9H); 4.24 (q,2H);
6.50 (d,lH): 7.60 (d,lH); 8.82 (s,2H).
Infra red (paraffin mull): 2960, 1730, 1645, 1590, 1485, 1440, 1320, 1185, 1155 cm~
EXAMP~E 6 This 2xarnple illustrate the preparation of ethyl trans -2,2-dirnethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl~
cyclopropane carboxylate.
A solution of n~butyllithium ~lO.Gcm3 of a 1.55~1 solution in hexane) was added slowly to a stirred solution of prop~2-yl triphenyl phosphonium iodide (7.lg) in dry tetrahyclrofuran (20cm3) at the ambient temperature under a nitrogen atmosphere and the resultant mixture stirred for a further 15 minutes a~ter ~Ihich a solution of ethyl trans 3-~2-(2-methylprop-2-yl)pyrimidin-5-yl~propenoate (3.2g) in dry tetrahydrofuran (25cm3) was added dropwise at -5C.
After stirring for a further period of 30 minutes during which time the mixture warmed to the ambient te~perature it was kept at the ambient temperature for 16 hours. The mixture was partitioned between water (300cm3) and diethyl ether (200cm3) and the aqueous phase extracted witl1 ether (2 x 200cm3) and the extracts combined with the ethereal phase. After washing with water (2xlOOcm3) and drying over anhydrous magnesium sulphate, the ether was removed by evaporation under reduced pressure to yield a residual oil which was subjected to dry column chromatography using a silica column eluted ~irst with dichloromethane (to remove triphenyl phosphine) and then with a mixture of dichloromethane (100 parts by volume) and e~hyl acetate (5 parts by volume) to yield ethyl trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl~cyclopropane carboxylate (2.~g), the iden~ity of ~.~hich was confi med by ~5 inra red and n.m.r. spectroscopy.
H NMR (CDC13) ~ : 0.99 (s,3H); 1.31 (t,3H); 1.40 (s,12H);
1.96 (d,lH); 2.54 (d,lH); 4.2 (q,2H);
8.5 (s,2H) Infra red (liquid film) : 2960, 1730, 1485, 1450, 1420, 1260, 1180, 1165 c~-l.
Mass spectroscopy (M+) : 276 - 21 - ~ ~7~7 This Example illustrates the preparation of trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl3 cyclopropane carboxylic acid.
A solution of ethyl trans-2,2-dimethyl-3-[2-(2-methyl-S prop-2-yl)pyrimidin-S-yl]cyclopropane carboxylate (2.6g) in ethanol (50cm3j was mixed with a solution of sodium hydroxide (l.Og) in water (50cm3) and the mixture stirred at the ambient temperature for 5 hours. After removal of the bulk of the ethanol by evaporation under reduced pressure the pH of the residual mixture was adjusted to 3 with dilute hydrochloric acid. The mixture was extracted with diethyl ether (2 x 200cm3), and the combined extracts washed with water and dried over anhydrous magnesium sulphate. Evaporation of the ether under reduced pressure yielded trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl]cyclopropane carboxylic acid (2.lg), melting point 16~-9C.
E~ NMR (CDC13)~ : 1.03 (s,311); 1.41 (s,9H), 1.4~ (s,3EI);
2.02 (d,lEI); 2.6 td,lH); a.57 (s,2H) Infra red (paraffin mull): 2940, 1700, 1485, 1430, 1335, 1250, 1230, 1210 cm~
Mass spectroscopy (M+) : 24~
This Example illustrates the preparation of 3-phenoxybenzyl trans-2,2-dimethy.-3-~2-(2-met'nylprop-~-yl)pyrimidin-S-yl]cyclopropane carboxylate.
A mixture of trans-2,2-dimethyl-3-[2-(2-methylprop 2-yl) pyrimidin-5-yl]cyclopropane carboxylic acid ~ 22 -(500mg), 3-phenoxybenzylbromide (552mg), anhydrous potassium carbonate (304mg) and acetone (lOcm3) was heated at ~he re1ux temperature for 2 hours with s~irring after which it was ~ept at the ambient temperature for 16 hours.
After removing the solid precipitate by filtration the filtrate was concentrated by evaporation under reduced pressure. ~he residual oil was subjected to high performance liquid chromatography (Gilson) using a silica column and, as eluent, a mixture of dichloromethane (100 parts by volume) and ethyl acetate (2 par~s by volume).
The product, 3-phenoxybenzyl trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)-pyrimidin-5-yl]cyclopropane carboxylate (~OOmg) was obtained as an oil and identification was confirmed by n.m.r. and infra red lS spectroscopy.
H NMR ~CDC13) ~ : 0.98 (s,3H); 1.40 (s,12H), 2.02 (d,lII) 2.56 (d,lH), 5.15 (s,2H); 6.~-7.5 (m~9H), Infra red (liquid film) : 2960, 1730, 1590, 1490, 1260, 1220, 1160 cm~
~lass spectroscopy (M+) : 430 This Example illustrates the preparation of 4-allyl-2,3,5,6-tetrafluorobenzyl trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl~cyclopropane caroboxylate.
Dicyclohexylcarbodiimide (420mg) was added in portions to a stirred mixture of trans-2,2-dimethyl-3-~2-(dimethyl-prop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate (504mg), 4-allyl-2,3,5,5-tetrafluorobenzyl alcohol (462mg -containing a minor amount of isomeric 2-allyl-3,4,5,6-tetrafluorobenyl alcohol), 4-dimethylamino pvridine (5mg) and dry dichloromethane (lOcm3) at the ambient temperature and the resultant mixture stirred for 2 further period of 105 minutes after which it was kept at the ambient temperature for 16 hours. The solid precipitate was removed by filtration, washed with ether and the washings combined with the filtrate. Ater removal of the solvent by evaporation under reduced pressure the residual oil was subjected to HPLC (Gilson) using a silica column and, as eluent, a mixture of dichloromethane (100 parts by volume) and ethyl acetate (2 parts by volume) to give a product consisting of 94~ by weight of the 4-allyl-2,3,5,6-tetrafluorobenzyl ester and 6% by weight of the 2-allyl-3,4,5,6-tetrafluorobenzyl ester of trans-Z,2-dimethyl-3-C2-(2-methylprop-2-yl~pyrimidin-5-yl]cyclopropane carboxylic acid (650mg), as an oil which solidified on standing, melting point 64-66C. The identification was confirmed by n.m.r., infra re~ and mass spectroscopic analysis.
lH NMR (CDC13) ~ : 0.99 (s,3~); 1.39 (s,12H); 1.96 (d,lH);
2.56 (d,lH); 3.5 (m,2H); 4.9-5.3 (m,4H);
5.6-6.1 (m,lH); 8.48 (s,2H).
~nfra red (paraffin mull): 2960, 2930, 2860, 173S, 1490, 1460, 1440, 1420, 1330, 1150 cm~
Mass spectroscopy ~M+) : 450 $XAMPLE 10 By the use of a procsdure similar to that described in Example 8 4-metnyl-2,3,5,6-tetrafluorobenzyl trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl~
cyclopropane car~oxylate was obtained as a colourless oil from the carboxylic acid and the benzyl bromide.
H ~MR (CDC13) ~ : 0.99 (s,3H); 1.39 (s,12H); 196 (a~lH);
2.30 (m,3H); 2.56 (d,lH); 5.28 (s,2H);
8.48 (s,2H) Infra red (liquid film) : 2960, 1740, 1495, 1420, 1290, 1155, 1075 cm~l.
Mass spectroscopy (M~) : 424 By the use of a procedure similar to that described in Example 9 th~ following esters were obtained:
(a) 6-phenoxypyrid-2-ylmethyl trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl~cyclopropane carboxylate from the carboxylic acid and 6-phenoxypyrid-2-ylmethanol.
H ~MR (CDC13) ~ : 1.01 (s,3H); 1.41 (s,12H); 2.08 (d,lH);
2.58 (d,lH); 5.18 (s,2H); 6.7-7.8 (m,8H);
. 8.50 (s,2H) Infra red (liquid ilm): 2960, 1730, 1600, 1580, 1490, 1540, 1250, 1160 cm~
Mass spectroscopy (E~+) : 431 f~
(b) 2-methyl-3~phenylbenzyl trans-2,2-dim0thyl-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate from the carboxylic acid and 2-methyl-3-phenylbenzyl alcohol.
H NMR (CDC13) ~ : 0.99 (s,3H); 1040 (s,12H), 2-0~ (~,lH);
2.25 (s,3H); 2060 (d,lH); 5 27 (s,2H);
(+)-l-cyano-1-(6-phenoxypyrid-2-yl)methyl (+)-trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)pyrimidin 5-yl]
cyclopropane carboxylate (hareinafter "Compound VI").
2-methyl-3-phenylbenzyl (+)-trans-2,2-dimethyl-3-[2-methyl-prop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate (hereinafter "Compound VII").
4-fluoro-3-phenoxybenzyl (+)-trans-2,2-dimethyl-3-[2-methylprop-2-yl)pyrirnidin-5-yl~cyclopropane carboxylate (hereinafter "Compound VIII").
(+)-1-cyano-1-(6-phenoxypyrid-2-yl)methyl (+)-trans-2,2 dimethyl-3-(2-prop-2-yl-pyrimidin-5-yl)cyclopropane carboxylate (hereinafter "Compound IX").
(+)-l-cyano-1-(6-phenoxypyrid-2-yl)methyl (+)-trans-2,2-dimethyl-3-(2-cyclohexylpyrimidin-5-yl)cyclopropane carboxylate (hereinafter "Compound X").
~ l-cyano-1-(6-phenoxypyrid-2-yl)methyl (+)-trans=2,2-dimethyl-3-(2-cyclopropylpyrimidin-5-yl)cyclopropane carboxylate (hereinafter "Compound XI").
(+)-1-(6-phenoxypyrid-2-yl)ethyl (+)-trans-2,2-dimelhyl-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl)cyclopropane carboxylate (hereinafter "Compound XII").
pentafluorobenzyl (+)-trans-2,2-dimethyl-3-[2-(2-methyl-prop-2-yl)pyrimidin-5-yl~cyclopropane carboxylate (hereinater "Compound XiII").
(+)~X-ethynyl-3-phenoxybenzyl (+)-trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate (hereinafter "Compound XIV").
~2,~
4-methoxymethyl-2,3,5,6-tetrafluorobenzyl (+)-trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl~cyclo-propane carboxylate (hereinafter '`Compound XV").
2 methyl-3-phenylbenzyl (+)-trans-2,2-dimethyl-3-(2-prop-2-ylpyrimidin-5-yl)cyclopropane carboxylate (hereinater "Compound XVI").
The insecticidally active compounds of the invention accordi~g to Formula I are esters and may be prepared by conventional esterification processes, of which the following are examples.
(a) An acid of formula:-O
R2 ~ ~ CH - /CH-~-Q II
C~
where Q represants the hydroxy group and R2 has any of the meanings given hereinabove, may be reacted directly with an alcohol of formula Rl-OH
5III) where Rl has any of the meanings glven hereinabove, the reaction preferably taking place in the presence of an acid catalyst, for exampls, dry hydrogen chloride, or a dehydrating agent, such as for example, dicyclohexyl carbodiimide.
(b) An acid halide of formula II where Q .epresents a halogen atom, preferably a chlorine atom, and R2 has any of the meanings yiven hereinabove, may bs reacted with an alcohol of formula III, the reaction p eferzbly taking place in the presence of a base, for example, pyridine, alXali metal hydroxide or carbonate, or al~ali metal alkoxlde.
(c) An acid of formula II where Q represents the hydroxy group or, preferably, an alkali metal salt thereo, may be reacted with halide of formula Ql-Rl (IV) wherein Ql represents a halogen atom, preferably the cnloxine atom, and Rl has any of the meanings given hereinabova, or with the quaternary ammonium salts ~ derived from such halides with tertiary amines, for example pyridine, or trialXyl a~ines such as triethylamine.
(d) A lower alkyl ester of formula (II) where Q represents a lower alkoxy group containing up to six carbon atoms, preferably the methoxy or etho~y group, and R2 has any of the meanings given hereinabove, is heated with an alcohol of formula III to efect a transesterification reaction. Preferably the process is performed in the presence of a suitahle catalyst, for example, an alXali metal al~.oxide, such as sodium metho~ide, or an alkylated titanium derivative, such as tetramethyl titanate.
A'l of these conventional processes for the preparation of esters may be carried out using solvents and diluents for the various reactants where appropriate, ~.Q~
may be accelerated or lead to higher yields of ~roduct w~en performed at elevated temperatures or in the presence of appropriate catalysts, for example phase-transer catalysts.
The preparation of individual isomers may be carried out in the same manner but commencing from the corres-ponding individual isomers of compounds of formula ~I.
T~ese may be obtained by conventional isomer separation techniques from mixtures of isomers. Thus cls and trans isomers rnay be separated by fractional crystallisation of the carboxylic acids or salts thereor, whilst the various optically active species may be obtained by fractional crystallisation of salts of the acids with optically active amines, followed by regeneration of the optically pure acid. The optically pure isomeric form of the acid (or its equi~alent acid chloride or ester) may then be reacted with the appropriate alcohol to produce a compound of formula I
in the form of an individually pure isomer thereof.
The compounds of formula I may be used to combat and control infestations of insect pests and also other invertebrate pests, for example, acarine pests. The insect and acarine pests which may be combatted and controlled by the use of the invention compounds include those pests associated with agriculture (which term 1ncludes the growing of crops for food and fibre products, horticulture 1~ and animal husbandry), forestry, the stora~e of products of vegetable origin, such as fruit, grain and timber, and also those pests associated with the transmission of fliseases of man and animals.
In order to apply the compounds to the locus of the pests they are usually formulated into compositions which include in addition to the insecticidally active ingredient or ingredients of formul.a I suitable inert diluent or carrier materials, and/or surface active agents. The cor.lpositions may also comprise another pesticidal material, for example another insecticide or acaricide, or a fungicide, or may also comprise an insecticide synergist, such as for example dodecyl imidazole, safroxan, or piperonyl butoxide.
The compositions may be in the form of dusting powders wherein the active ingredient is mixed with a solid diluent or carrier, for example Xaolin, bentonite, kieselguhr, or talc, or they may be in the form of granules, wherein tne active ingredient is absorbed in a porous granular m2terial for example pumice.
Al-ternatively the compositions may be in the form of liquid preparations to be used as dips or sprays, whi~h are generally aqueous dispersions or emulsions of the active ingredient i.n the presencQ of one or more Xnown wetting agents, dispersing agents or emulsifying agents (surface active agents).
Uetting agents, dispersing agents and emulsifying agents may ~e of the cationic, anionic or non-ionic typeO
6uitable agents of the cationic type include, for example, quaternary ammonium com c,unds, for example cetyltrimethyl ammonium bromide. Suitable agents of the anionic type include, Eor exa~.ple, soaps, salts of aliphatic monoestars of su].phuric acid, for example sodium lauryl sulphate, salts of sulphonated aromatic compounds, for example sodium dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, or butylnaphthalene sulphonate, and a mixture of the sodium salts of diisopropyl- and triiso-propylnaphthalene ~ulphonates. Suitable agents of the non-ionic type include, ~or example, the condensation products of ethylene oxide with fatty alcohols such as oleyl alcohol or cetyl alcohol, or with alkyl phenols such as octyl phenol, nonyl phenol and octyl cresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, the condensation products of the said partial esters with etllylene oxide, and the lecithins.
Ths compositions may be prepared by dis301ving the active ingredient in a suitable solvent, ror example, a ketonic solvent such as diacetone alcohol, or an aromatic solver,t such as trimethylben~ene and adding the mixture so obtained to water which may cor.tain one or more known wetting, dispersing or emulsifying agents.
Other suitable organic solvenis are dimethyl formam.de, ethylene dichloride, isopropyl alcohol, propyiene glycol and other glycols, diacetone alcohol, toluene, kerosene, ~whlte oil, methylnaphthalene, xylenes and trichloroe~hylene, ~J-methyl-2-pyrrolidone and tetrahydrofurfuryl alcohol (T~FA).
The compositions which are to be used in the form of aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient or ingredients, the said concentrate to be diluted with water before use. These concentrates are often required to withstand storage for prolo~ged periods and after such storage, to be capable of dilution with water to form aqueous preparations which remain homogenous for a sufficient time to enable them to be applied by conventional spray equipment. The concentrates may contain 10-85% by weight of the active ingredient or ingredients. ~1hen diluted to form aqueous preparations such preparations may contain varying amounts of the active ingredient depending upon the purpose for which Lhey are to be used. For agricultural or horticultural purposes, an a~ueous preparation containing between O.OOOl~ and O.l~ by weight O;e the active ingredient is particularly useful.
In use the compositions are applied to the pests, to the locus of the pests, to the habitat of the pests, or to growing plants liable to infestation by the pests, by any of the known means or applying pesticidal compositions, for example, by dustinc~ or spraying.
The compositions of the invention are toxic to a variety of insect and other invertebrate pests, including, for example, the following:
Myzus persicae (aphids) Aphis fabae (aphids) Megoura viceae (aphids) Aedes aegypti (mosquitoes) Dysdercus fasciatus (capsids) Musca domestica (houseflies) Pieris brassicae (white butterfly, larvae) Plutella maculipennis (diamond back moth, larvae) Phaedon cochleariae (mustard beetle) _ Tetranychus cinnabarinus (carmine spider mite) Tetranychus urticae (red spider mites) ~onidiella spp. (scale insects) Trialeuroides spp. (white flies) Blattella germanica (coc~roaches) -Spodoptera littoralis (cotton leaf worm) Heliothis virescens (tobacco budworms) Chortiocetes terminifera (locusts) Diabrotica spp. (rootworms) Agrotis spp. (cutworms) Chilo partellus (mai3e stem borers) The compounds of formula I and compositions comprising them have shown themselves to be particularly useful in controlling acarine pests o~ plants such as red mites and rust mites as well as lepidopteran pests of cotton, for example Spodoptera spp. and Heliothis spp. The compounds may also be used to combat pests which inhabit the soil, for example Diabrotica spp. They ~.ay also be useful in combating insect and acarine E~ests which infest domestic animals, such as Lucilia sericata, and ixodid ticks such as Boophilus 5pp., Ixodes spp., mblyomma spp., Rhipicephalus spp., and Dermaceutor spp. ~ney may be effective in combating both susceptible and resistant strains of these pests in their adult, larval and intermediate sta~es of growth, and may be applied to the infested host an~mal by topical, oral or parenteral administration.
The following Examples illus-trate various aspects o~
this invention. In the preparation Examples the products were usually identified and characterised 'Dy means of nuclear magnetic resonance spectroscopy and infra red spectroscopy. In each case where a product is specifically named its spectral characteristics are consistent with the assigned structure.
EXA~PLE 1 This Example illustrates the preparation of pivalamidine hydrochloride.
A s-tirred mixture of trimethylacetonitrile (43g;
0.51M) and dry ethanol (24g, 0.51M) was cooled using an ice/salt bath whilst dry hydrogen chloride gas was passed into the mixture over a period of 90 minutes, until a total of 21gms had been ta~en up. The mixture was then kept for 2 days at the ambient temperature a ter w~ich it was diluted with dry diethyl ether (500cm3) to precipitate ethyl trimethyl ace-timidate hydrochloride which was collected by filtration (34.5g). To this was added portionwise a solution of dry ammonia gas (6g) in dry ethanol (50cm3) with vigorous stirring. The solid gradually dissolved during the coursa of the addition and the resultant solution was kept at the ambient temperature for 20 hours aEter which t~e solvent was removed by evaporation under reduced pressure and the residual solid washed with diethyl ether to yield pivalamidine hydrochloride (23g).
EX~I~PLE 2 This Example illustrates the preparation of 5-bromo-2-(2-methylprop-2-yl)pyrimidine-4-carboxylic acid.
A solution of sodium ethoxide in ethanol (14.5cm3 o the solution obtained by dissolving sodium (1.38g) in dry ethanol (24cm3)) was added carefully to a stirred mixture of pivalamidine hydrochloride (5.18g) and dry ethanol (5cm3) at 40C. After stirring the mixture for a further 10 minutes a solution of mucobrcmic acid (5.4cm3 of the solution obtained by dissolvir.g mucobromic acid (5.16g) in dry ethanol (3.0cm3)) was added to the mixture resulting in an exothermic reaction during which the temperature rose to 65C. After a period the temperature had reduced to 50C
and the remainder of the sodium ethoxide solution and the remainder of mucobromic acid solution were added. ~he reaction temperature was maintaired at ;0C for 1 hour by external heating, after which the insoluble portion was removed by filtration at that temperature, washed wit'n ethanol and the washings and filtrate combined. After removing the solvent by evaporation under reduced pressure the residual solid was washed with dilute hydrochloric acid (2M, lOcm3), with water and dried to yield S-bromo-2(2-methylpro-2-yl)pyrimidine-4-carboxylic acid (3.8g), melting point 142-144C (with decomposition) ~.m.r and infrared spectra were consistent with this identification.
H ~MR (CDC13) ~ 5 (s,9H); 9.05 (s,lEI); 9.44 (broad s, lH).
lS Infra red (paraffin mull) : 2940, 286G, 2500 (broad), 1710, 1570, 1370, 1305, 1290, 1220, 1190, 1175, 750, 680 cm~
EXAMPL~ 3 This Example illustrates the preparation of 5-bromo-2-(2-methylprop-2-yl)pyrimidine.
5-Bromo-2-(2-methylprop-2-yl)p~rimidine-4-carboxylic acid (l.Og) was heated with stirring at 145C after which the decarboxylated product was obtained by distillation using a Kugelrohr apparatus under water pump pressure. The distillate solidified on cooling to yield 5-bromo-2-(2-methylprop-2-yl)pyrimidine (0.6g) melting point 50-51~C.
N.m.r. and infra-red spectra were consistent with this identification.
1~ nmr (CDC13) ~ : 1.39 (s,9H); 8.71 (s,2E~).
Infra red (paraffin mull) : 2940, 2860, 1530, 14SO, 1420, 1170, 1010, 810, 640 cm-l This ~xample illustrates the preparation of 2-(2-methylprop-2-yl)pyrimidine-5-carboxaldehyde.
A solution of 5-bromo-2-(2-methylprop-2-yl)pyrimidine (7.6g, 0.035M) in dry tetrahydrofuran (SOcm3) was added in small portions to magnesium turnings (0.95g, Grignard grade) in the presence of a few crystals of iodineO Ths rate of addition was controlled by the rate of the exothermic reaction. ~Ihen the additi.on was complete the mixture was warmed to complete the reaction. After cooliny t'he mixture to 5C, a solution of dimethyl formamide (2.58g) in tetrahydrofuran (15ml) was added thereto dropwise. The mixture was allowed to warm to the ambient temperature with stirring ovar a period of 2 hours and ~ept for 16 hours without stirring. After adding water (5cm3) to the mixture the tetrahydrofuran was removed by evaporation under reduced pre~sure and the residue partitioned between dilute aqueous ammonium c'hlorid0 solution (lOOcm3) and diethyl ether (150cm3). The aqueous phase was extracted with ether (150cm3) and t'he extract combined with the ether phase, washed with water, and dried over anhydrous magnesium sulphate. Evaporation of the ether under reduced pressure yielded an oily solid residue ($.8g) which was purified by dry column chromatography using a silica column eluted with a mixture of methylene chloride (100 parts by volume) al1d ethyl acetate (2 parts by volume) to give 2-(2-methylprop-2-yl)pyrimidine-5-carboxaldehyde (3.4g) melting point S2-83C.
Infra red (paraffin mull): 2940, 2860, 1700, 1590, 1430, 1230, 1150, 860, 650 cm~
E~AMPLE 5 This Example illustrates the preparation of ethyl 3-[2-(1,1-dimethylethyl)pyrimidin-5-yl] propenoate.
A solution of 0,0-diethyl ethoxycarbonyl-methylphosphonate (3.93g) in dry diethyl ether (20cm3) was added dropwise to a stirred suspension of sodium hydride (0.54g of a 50% oil dispersion) in dry S diethyl ether (30cm3) at -5C and the mixture stirred thereafter for a further period of 90 minutes. A solution of 2-(2-methylprop-2-yl)pyrimidine-5carboxaldehyde (2.88g) in dry diethy~ ether (40cm3) ~as added dropwise to this stirred mixture at 0C, the resultant mixture allowed to warm to the ambient temperature with stirring over 2 hours after which it was kept at the ambient temperatures for 16 hours. The mixture was partitioned between water (150cm3) and diethyl ether (250cm3), the aqueous phase extracted with ether (2~0cm3) and the extracts combined with the ethereal phase. After washing with water (200cm3) and drying over anhydrous magnesium sulphate, the solvent was evaporated under reduced pressure and residual oil subjected to dry column chromatography using a silica column and, as eluent, dichloromethane containing 5% v/
ethyl acetate, to yield ethyl 3-[2-(2-methylprop-2-yl)pyrimidin-5-yl]propenoate (3.6g) which solidiied on standing, melting point 43-45C. ~T.m.r.
and inra-red spectral data indicate the product as consisting of the trans isomer.
lrA ~MR (CDC13) ~ : 1.35 (t,3H); 1.42 (s,9H); 4.24 (q,2H);
6.50 (d,lH): 7.60 (d,lH); 8.82 (s,2H).
Infra red (paraffin mull): 2960, 1730, 1645, 1590, 1485, 1440, 1320, 1185, 1155 cm~
EXAMP~E 6 This 2xarnple illustrate the preparation of ethyl trans -2,2-dirnethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl~
cyclopropane carboxylate.
A solution of n~butyllithium ~lO.Gcm3 of a 1.55~1 solution in hexane) was added slowly to a stirred solution of prop~2-yl triphenyl phosphonium iodide (7.lg) in dry tetrahyclrofuran (20cm3) at the ambient temperature under a nitrogen atmosphere and the resultant mixture stirred for a further 15 minutes a~ter ~Ihich a solution of ethyl trans 3-~2-(2-methylprop-2-yl)pyrimidin-5-yl~propenoate (3.2g) in dry tetrahydrofuran (25cm3) was added dropwise at -5C.
After stirring for a further period of 30 minutes during which time the mixture warmed to the ambient te~perature it was kept at the ambient temperature for 16 hours. The mixture was partitioned between water (300cm3) and diethyl ether (200cm3) and the aqueous phase extracted witl1 ether (2 x 200cm3) and the extracts combined with the ethereal phase. After washing with water (2xlOOcm3) and drying over anhydrous magnesium sulphate, the ether was removed by evaporation under reduced pressure to yield a residual oil which was subjected to dry column chromatography using a silica column eluted ~irst with dichloromethane (to remove triphenyl phosphine) and then with a mixture of dichloromethane (100 parts by volume) and e~hyl acetate (5 parts by volume) to yield ethyl trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl~cyclopropane carboxylate (2.~g), the iden~ity of ~.~hich was confi med by ~5 inra red and n.m.r. spectroscopy.
H NMR (CDC13) ~ : 0.99 (s,3H); 1.31 (t,3H); 1.40 (s,12H);
1.96 (d,lH); 2.54 (d,lH); 4.2 (q,2H);
8.5 (s,2H) Infra red (liquid film) : 2960, 1730, 1485, 1450, 1420, 1260, 1180, 1165 c~-l.
Mass spectroscopy (M+) : 276 - 21 - ~ ~7~7 This Example illustrates the preparation of trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl3 cyclopropane carboxylic acid.
A solution of ethyl trans-2,2-dimethyl-3-[2-(2-methyl-S prop-2-yl)pyrimidin-S-yl]cyclopropane carboxylate (2.6g) in ethanol (50cm3j was mixed with a solution of sodium hydroxide (l.Og) in water (50cm3) and the mixture stirred at the ambient temperature for 5 hours. After removal of the bulk of the ethanol by evaporation under reduced pressure the pH of the residual mixture was adjusted to 3 with dilute hydrochloric acid. The mixture was extracted with diethyl ether (2 x 200cm3), and the combined extracts washed with water and dried over anhydrous magnesium sulphate. Evaporation of the ether under reduced pressure yielded trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl]cyclopropane carboxylic acid (2.lg), melting point 16~-9C.
E~ NMR (CDC13)~ : 1.03 (s,311); 1.41 (s,9H), 1.4~ (s,3EI);
2.02 (d,lEI); 2.6 td,lH); a.57 (s,2H) Infra red (paraffin mull): 2940, 1700, 1485, 1430, 1335, 1250, 1230, 1210 cm~
Mass spectroscopy (M+) : 24~
This Example illustrates the preparation of 3-phenoxybenzyl trans-2,2-dimethy.-3-~2-(2-met'nylprop-~-yl)pyrimidin-S-yl]cyclopropane carboxylate.
A mixture of trans-2,2-dimethyl-3-[2-(2-methylprop 2-yl) pyrimidin-5-yl]cyclopropane carboxylic acid ~ 22 -(500mg), 3-phenoxybenzylbromide (552mg), anhydrous potassium carbonate (304mg) and acetone (lOcm3) was heated at ~he re1ux temperature for 2 hours with s~irring after which it was ~ept at the ambient temperature for 16 hours.
After removing the solid precipitate by filtration the filtrate was concentrated by evaporation under reduced pressure. ~he residual oil was subjected to high performance liquid chromatography (Gilson) using a silica column and, as eluent, a mixture of dichloromethane (100 parts by volume) and ethyl acetate (2 par~s by volume).
The product, 3-phenoxybenzyl trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)-pyrimidin-5-yl]cyclopropane carboxylate (~OOmg) was obtained as an oil and identification was confirmed by n.m.r. and infra red lS spectroscopy.
H NMR ~CDC13) ~ : 0.98 (s,3H); 1.40 (s,12H), 2.02 (d,lII) 2.56 (d,lH), 5.15 (s,2H); 6.~-7.5 (m~9H), Infra red (liquid film) : 2960, 1730, 1590, 1490, 1260, 1220, 1160 cm~
~lass spectroscopy (M+) : 430 This Example illustrates the preparation of 4-allyl-2,3,5,6-tetrafluorobenzyl trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl~cyclopropane caroboxylate.
Dicyclohexylcarbodiimide (420mg) was added in portions to a stirred mixture of trans-2,2-dimethyl-3-~2-(dimethyl-prop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate (504mg), 4-allyl-2,3,5,5-tetrafluorobenzyl alcohol (462mg -containing a minor amount of isomeric 2-allyl-3,4,5,6-tetrafluorobenyl alcohol), 4-dimethylamino pvridine (5mg) and dry dichloromethane (lOcm3) at the ambient temperature and the resultant mixture stirred for 2 further period of 105 minutes after which it was kept at the ambient temperature for 16 hours. The solid precipitate was removed by filtration, washed with ether and the washings combined with the filtrate. Ater removal of the solvent by evaporation under reduced pressure the residual oil was subjected to HPLC (Gilson) using a silica column and, as eluent, a mixture of dichloromethane (100 parts by volume) and ethyl acetate (2 parts by volume) to give a product consisting of 94~ by weight of the 4-allyl-2,3,5,6-tetrafluorobenzyl ester and 6% by weight of the 2-allyl-3,4,5,6-tetrafluorobenzyl ester of trans-Z,2-dimethyl-3-C2-(2-methylprop-2-yl~pyrimidin-5-yl]cyclopropane carboxylic acid (650mg), as an oil which solidified on standing, melting point 64-66C. The identification was confirmed by n.m.r., infra re~ and mass spectroscopic analysis.
lH NMR (CDC13) ~ : 0.99 (s,3~); 1.39 (s,12H); 1.96 (d,lH);
2.56 (d,lH); 3.5 (m,2H); 4.9-5.3 (m,4H);
5.6-6.1 (m,lH); 8.48 (s,2H).
~nfra red (paraffin mull): 2960, 2930, 2860, 173S, 1490, 1460, 1440, 1420, 1330, 1150 cm~
Mass spectroscopy ~M+) : 450 $XAMPLE 10 By the use of a procsdure similar to that described in Example 8 4-metnyl-2,3,5,6-tetrafluorobenzyl trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl~
cyclopropane car~oxylate was obtained as a colourless oil from the carboxylic acid and the benzyl bromide.
H ~MR (CDC13) ~ : 0.99 (s,3H); 1.39 (s,12H); 196 (a~lH);
2.30 (m,3H); 2.56 (d,lH); 5.28 (s,2H);
8.48 (s,2H) Infra red (liquid film) : 2960, 1740, 1495, 1420, 1290, 1155, 1075 cm~l.
Mass spectroscopy (M~) : 424 By the use of a procedure similar to that described in Example 9 th~ following esters were obtained:
(a) 6-phenoxypyrid-2-ylmethyl trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl~cyclopropane carboxylate from the carboxylic acid and 6-phenoxypyrid-2-ylmethanol.
H ~MR (CDC13) ~ : 1.01 (s,3H); 1.41 (s,12H); 2.08 (d,lH);
2.58 (d,lH); 5.18 (s,2H); 6.7-7.8 (m,8H);
. 8.50 (s,2H) Infra red (liquid ilm): 2960, 1730, 1600, 1580, 1490, 1540, 1250, 1160 cm~
Mass spectroscopy (E~+) : 431 f~
(b) 2-methyl-3~phenylbenzyl trans-2,2-dim0thyl-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate from the carboxylic acid and 2-methyl-3-phenylbenzyl alcohol.
H NMR (CDC13) ~ : 0.99 (s,3H); 1040 (s,12H), 2-0~ (~,lH);
2.25 (s,3H); 2060 (d,lH); 5 27 (s,2H);
7.1-7.5 (m,8H); 8050 (s,2H)O
Infra red (liquid film): 2960, 1730, 1485, 1420, 1160, 760, 705 cm~
Mass spectroscopy (M+) : 423 (c) ~-cyano~3-phenoxy~enzyl trans-2,2-dimethyl-3-~2-(2-methyl-prop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate from the carboxylic acid and ~-cyano-3-phenoxyben7yl alcohol.
H ~MR (CDC13) ~ : 0.99 (s); 1.04 (s); 1.35 (s); 1.39 (s);
1.~5 (g); 2.05 (m); 2.6 (m); 6.42 (s);
6.44 (s); 7.26 (m); 8.46 (s); 8.50 (s).
(Integra~ion consistent with 2:1 mixture of diastereoisomers).
Infra red (liquid fim): 2960, 1740, 1590, 1485, 1250, 1140, 695 cm~
Mass spectroscopy (M+) : 455 (d) 1-cyano-1-(6-phenoxypyrid-2-yl)methyl ~rans-2,2-dimethyl-3-~2-~2-methylprop-2-yl)pyrimidin-5-yl;
cyclopropane carboxylate from the carboxylic acid and l-cyano~ (6-phenoxypyrid-2-yl)methanol.
H MMR (CDC13) ~ : 1.00 (s); 1.02 (s); 1.35 (s); 1.40 (s);
2.1 (m); 2.6 (m); 6.4 (3s); 6.9 (d);
7.2 (m), 7.2 ~dd), 8.50 (2s).
(Integration consistent with lol mixture of diastereoisomers).
Infra red (liquid film); 2960, 1745, 1595, 1490, 1450, 1260, 1140, 695 cm~
Mass spectroscopy (M+) : 456 (e) 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl (+)-trans-2,2-dimethyl-3-C2-(2-methylprop-2-yl)pyrimidin-5-yl)-2,2-dimethylcyclopropane carboxylate from the carboxylic acid and 4-methoxymethyl-2,3,5,6-tetra fluorobenzyl. alcohol.
lH ~MR (CDC13) ~ : 0.99 (s,3H); 1.40 (2s,121l), 1.95 (d,lH);
2.55 (d,lH); 3.40 (s,3~); 4.50 (m,2H);
5.30 (m,2H); 8.50 (s,2H) Inra red (parafin mull): 1735, 1595, 1490, 1295, 1150, 910, 880, 770 cm~
Mass spectroscopy (M+~ : 454 0 (~) (+)~ -phenoxypyrid-2-yl)ethyl (~)-trans-2,2-dimethyl-3-C2-(2-methylprop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate from the carboxylic acid and (+)-1-(6-phenoxypyrid-2-yl)ethanol.
lH ~MR (CDCl~) f~ : 1.0 (s); 1.33 (s); 1.40 (s); 1.5 (s);
1.8 (s); 2.05 (2d); 2.50 (2d); 5.85 (q), 6.7 (d); 7.2 (m); 7.65 (dd);
.50 (2s).
~ t~7 (Integration consistent with 3:2 mixture of diastereoisomers)0 Infra red ~liquid film): 2980, 1730, 1600, 1580, 1445, 1260, 1170, 990, 700 cm~
Mass spectroscopy (MH~) : 445 (g) 4-fluoro-3-phenoxybenzyl (+)-trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl)cyclopropane carboxylate from the carboxylic acid and 4-fluoro-3-phenoxybenzyl alcohol.
(h) pentafluorobenzyl (~)-trans-2,2-dimethyl-3 [2-(2-methylprop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate from the carboxylic acid and pentafluorobenzyl alcohol.
(g) (+)-~-ethynyl-3-phenoxybenzyl (+)-trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl)cyclopropane carboxylate f`rom the carboxylic acid and (~
ethynyl-3-phenoxybenzyl alcohol.
E~AMPLE 12 This Example illustrates the preparation of (+)-~-cyano-3-phenoxybenzyl (~)~trans-3-[2-(2-methylprop-2-yl) pyrimidin-5-yl]-2,2-dimethylcyclopropane carbo~ylate (Compound IV) and separat~on of its constituent pairs of enantiomeric isomers.
A stirred mixture of (~)-trans-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl]-2,2-dimethylcyclopropane carboxylic acid (3.2g), 3-phenoxybenzaldehyde cyanhydrin (3.8g, contaminated with ca. 20~ 3-phenoxybenzaldehyde), ~-dimethylaminopyridine (lOOmg) and dichloromethane (lOOcm3) was treated with portions of dicyclohexyl '`31. ~ L~ 7 carbodiimide (2.~g) at the ambient temperature (ca. 24C).
After stirring for two hours the mixture was kept at the ambient temperature for 1~ hours, filtered and the collected solids washe,d with dichloromethane. ~he combined filtrate and washings were concentrated by evaporation of the solvent under reduced pressure and the residual oil purified by h.p.l.c. (Gilson) using a silica column eluted with a mixture of dichloromethane (100 parts by volume) and ethyl acetate (5 parts by volume). The initial fractions yielded a mixture of the ~esired product with 3-phenoxybenzalaehyde, the later fractions gave pure (+) ~-cyano-3-phenoxybenzyl (~)-trans-3-[2-(2-methylprop-2-yl) pyrimidin-5-yl]-2/2-dimethylcyclopropane carboxylate (5.3g) in the form of a gum consistin~ of a mixture of two racemic pairs of enantiomeri.c isomers in a ratio of 2~ he initial fractions were rechromatographe~ using a 2.5cm silica column and the ~ame eluent at a rate of 30cm3/minute to give the faster running (less polar) pair of enantiomeric isomers (120mg). The more polar (aster running) pair of enantiomeric isomers (21mg) was obtained by similar rechromatography of the later ractions (containing the 2:1 mixture (A) of isomer pairs). The product consisted of a 95:5 mixture of the more polar and less polar isomers. Recombination of rejected ractions and evaporation ~ave a 7:1 mixture (B) of the less polar and more polar isomers.
In biolo~ical tests using adult red spider mites (Tetranychus urticae) on rench bean leaves the more polar pair of enantiomeric isomers was about ten times more effective (LC50=4.5ppm) than t'ne less polar pair (LC50=49ppm).
A mi~ture of the lsss polar and more polar pairs of enantiomeric isorners in a ratio of 7:1 (lOmg) was dissolved in isopropanol (O.lcm3) containing triethylamine (5~ by weiyht) was stirred at room temperature. After 22.5 hours the ratio was approximately 1:1 due to base induced epimerisation at the ~ carbon of the alcohol moiety.
H ~MR (CDC13) ~ o (A) 0.95 (s); 1.0 (s); 1-35 (s), 1.4 (s); 1.45 (s); 2.0 (2d);
S 2.6 (2d); 6.4 (2s); 7.2 (m); 8O45 (2s) (Integration consistent with 2:1 mixture of diastereoisomers).
(B) 1.0 (s,3H); 1.40 (s,9H); 1.45 (s,3H); 2.05 (d,lH); 2.55 (d,l~);
6.40 (s,lH); 7.2 (m,9EI); 8.40 (s,2H) Infra red (liquid film) : (A) 2960, 1740, 1590, 1490, 1445, 1250, 1140, 695 cm~
15 (B) 2960, 1740, 1585, 1480, 1445, 12~5, 1140, 695 cm~
EX~MPLE 13 Preparation of methyl (~)-trans-2,2-dimethyl-3-formyl cyclopropane carboxylate.
A mixture of methyl 2,2-dimethyl-3-(dimethoxymethyl)-20 cyclopropane carboxylate (95~ (T)-trans isomer: 40.0~), glacial acetic acid (120 cm3), acetone (160 cm3~ and water (280 cm3) was stirred at the ambient temperature for 5 hours, diluted with water (1500 cm3) and extracted with diethyl ether (1000 cm3). The aqueous residue was washed 25 with ether (2 x 500 cm3) and the washings and ex.racis washed with saturated sodium bicarbonate solution untll free of acidity. After drying tha ethereal solution over anhydrous magnesium sulphate the solvent was removed by evaporation to yield a residual oil which was purified by distillation and methyl ~ trans-2,2-dimethyl-3-formylcyclopropane carboxylate (28.5 g~ collected as the fraction boiling at 46-48C/).05 mm HgO
Preparation of (+)-trans methyl 3-[(E,Z)-2-methoxy-vinyl~-2~dimethylcyclopropane carboxylate.
Sodium hydride (obtained by washing a 50% oil dispersion (9D6 g) with n-hexane to remove the oil) was suspended in dry dimethylsulphoxide (150 cm3, freshly distilled from calcium hydride) and the suspension stirred under a dry nitrogen atmosphere at 3~-40C for 5 hours. A
solution o~ methoxymethyl triphenyl phosphonium chloricle ( 68 ~ 8 g) in dry dimethylsulphoxide (200 cm3) was added over 15 minutes whilst the reaction temperature was maintained at ca. 20C by external cooling. The solution o~ the ylid thus produced was added dropwise to a stirred solution of methyl (+)-trans-2,2-dimethyl-3-formylcyclopropane carboxylate (28.5 g, ~reshLy distilled) in 2~ dimethylsulphoxide (50 cm3) whilst keeping the reaction temperature ~t ca. 20C over a period of 2 hours. The mixture was stirred for a further 30 minutes and then Xept at the ambient temperature for 72 hours. r1ater (1500 cm3) was added, and the mixture extracted with diethyl ether 25 (1 x 1000 cm3), 2 x 500 cm3). The extracts were combined, washed with water (3 x 300 cm3) and dried over anhydrous magnesium sulphate. The solvent was remov~d by evaporation under reduced pressure ancl the residue triturated with petroleum ether (boiling range 60-80C, 150 cm3). The undissolved solid was removed by filtration and the filtrate evaporated to give a yellow oil (29.0 g) which was distilled under reduced pressure using a Kugelrohr apparatus to yield methyl t+)-trans-3-~(E,Z)-2-methoxy-vinyl]-2,2-dirtethylcyclopropane carboxylate (21.4 g), boiling point 64C/O.OS mm E~g.
lH NMR (CDC13) ~ : 1.13 (s); 1.24 (s); 1.26 ~s); 1.4 (m);
1.9 (m); 203 (m); 3.5 (s); 3.6 (s);
3066 (s); 401 (2d); 4.56 (2d); 600 (dd), 6.4 (d).
(Integration consistent with 2:1 mixture of (E) and (Z) isomers~.
10 Infra red (liquid film) : 2960, 1730, 1650, 14~0, 1270, 1235, 1170, 920 c~-l.
EXAMPL~ 15 This example illustrates the preparation of a mixture o methyl (~)-trans-3-[(E,Z)-2-dimethylamino-1-formyl-__ vinyl]-2,2-dimethylcyclopropane carboxylate and methyl (~)-trans-3-~(E,Z)-formyl-2-methoxyvinyl~-2,2-dimethylcyclo--propane carboxylate.
A solution of phosphoryl chloride (12.0 cm3) in 1,2-dichloroethane (10.0 cm3) was added dropwise to a stirred mixture of dimethylformamide (29.5 cm3) and 1,2-dichloroethane (100 cm3) at the ambient temperature.
When the addition was complete the mixture was stirred for a further 15 minutes and cooled to 15~C. To this mixture was added portionwise a solution of methyl (+)-trans-3-~(~,Z)-2-methoxyvinyl~-2,2-dimethylcyclopropane carboxylate (10.0 g) in 1,2-dichloroethane (80 cm3). The mixture was kept at the ambient temperature for 16 hours and solid anhydrous potassium carbonate (150 g) and ice added. ~nen the exothermic reaction had subsided the mixture was extracted with methylene chloride (2 x 300 cm3) and extracts combined and wa~hed with water (300 cm3). After drying over anhydrous magnesium sulphate the solvent was removed by evaporation under reduced pressure and the residual oil heated at 55C and 0.05 mm Hg in a Kugelrohr apparatus to remove the volatile components to yield a mixture containiny a minor amount of methyl (+)-trans 3-L(E,Z)-l-formyl-2-methoxy-vinyll-2,2-dimethylcyclopropane carboxylate and a major amount of methyl (+)-trans-3-~(E,Z)-l-dimethylamino-l-formylvinyl]-2,2-dimethyl-cyclopropane carboxylate (A), (10.3 g).
lH ~MR (CDC13) ~ : (A) 1.0 (s); 1.05 (s); 1~27 (s); 1030 (s); 2.0 (m); 3.18 (s); 3.37 (s), 3.68 (s); 3.70 (s); $.75 (broad 5);
Infra red (liquid film): 2960, 1730, 1485, 1420, 1160, 760, 705 cm~
Mass spectroscopy (M+) : 423 (c) ~-cyano~3-phenoxy~enzyl trans-2,2-dimethyl-3-~2-(2-methyl-prop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate from the carboxylic acid and ~-cyano-3-phenoxyben7yl alcohol.
H ~MR (CDC13) ~ : 0.99 (s); 1.04 (s); 1.35 (s); 1.39 (s);
1.~5 (g); 2.05 (m); 2.6 (m); 6.42 (s);
6.44 (s); 7.26 (m); 8.46 (s); 8.50 (s).
(Integra~ion consistent with 2:1 mixture of diastereoisomers).
Infra red (liquid fim): 2960, 1740, 1590, 1485, 1250, 1140, 695 cm~
Mass spectroscopy (M+) : 455 (d) 1-cyano-1-(6-phenoxypyrid-2-yl)methyl ~rans-2,2-dimethyl-3-~2-~2-methylprop-2-yl)pyrimidin-5-yl;
cyclopropane carboxylate from the carboxylic acid and l-cyano~ (6-phenoxypyrid-2-yl)methanol.
H MMR (CDC13) ~ : 1.00 (s); 1.02 (s); 1.35 (s); 1.40 (s);
2.1 (m); 2.6 (m); 6.4 (3s); 6.9 (d);
7.2 (m), 7.2 ~dd), 8.50 (2s).
(Integration consistent with lol mixture of diastereoisomers).
Infra red (liquid film); 2960, 1745, 1595, 1490, 1450, 1260, 1140, 695 cm~
Mass spectroscopy (M+) : 456 (e) 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl (+)-trans-2,2-dimethyl-3-C2-(2-methylprop-2-yl)pyrimidin-5-yl)-2,2-dimethylcyclopropane carboxylate from the carboxylic acid and 4-methoxymethyl-2,3,5,6-tetra fluorobenzyl. alcohol.
lH ~MR (CDC13) ~ : 0.99 (s,3H); 1.40 (2s,121l), 1.95 (d,lH);
2.55 (d,lH); 3.40 (s,3~); 4.50 (m,2H);
5.30 (m,2H); 8.50 (s,2H) Inra red (parafin mull): 1735, 1595, 1490, 1295, 1150, 910, 880, 770 cm~
Mass spectroscopy (M+~ : 454 0 (~) (+)~ -phenoxypyrid-2-yl)ethyl (~)-trans-2,2-dimethyl-3-C2-(2-methylprop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate from the carboxylic acid and (+)-1-(6-phenoxypyrid-2-yl)ethanol.
lH ~MR (CDCl~) f~ : 1.0 (s); 1.33 (s); 1.40 (s); 1.5 (s);
1.8 (s); 2.05 (2d); 2.50 (2d); 5.85 (q), 6.7 (d); 7.2 (m); 7.65 (dd);
.50 (2s).
~ t~7 (Integration consistent with 3:2 mixture of diastereoisomers)0 Infra red ~liquid film): 2980, 1730, 1600, 1580, 1445, 1260, 1170, 990, 700 cm~
Mass spectroscopy (MH~) : 445 (g) 4-fluoro-3-phenoxybenzyl (+)-trans-2,2-dimethyl-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl)cyclopropane carboxylate from the carboxylic acid and 4-fluoro-3-phenoxybenzyl alcohol.
(h) pentafluorobenzyl (~)-trans-2,2-dimethyl-3 [2-(2-methylprop-2-yl)pyrimidin-5-yl]cyclopropane carboxylate from the carboxylic acid and pentafluorobenzyl alcohol.
(g) (+)-~-ethynyl-3-phenoxybenzyl (+)-trans-2,2-dimethyl-3-~2-(2-methylprop-2-yl)pyrimidin-5-yl)cyclopropane carboxylate f`rom the carboxylic acid and (~
ethynyl-3-phenoxybenzyl alcohol.
E~AMPLE 12 This Example illustrates the preparation of (+)-~-cyano-3-phenoxybenzyl (~)~trans-3-[2-(2-methylprop-2-yl) pyrimidin-5-yl]-2,2-dimethylcyclopropane carbo~ylate (Compound IV) and separat~on of its constituent pairs of enantiomeric isomers.
A stirred mixture of (~)-trans-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl]-2,2-dimethylcyclopropane carboxylic acid (3.2g), 3-phenoxybenzaldehyde cyanhydrin (3.8g, contaminated with ca. 20~ 3-phenoxybenzaldehyde), ~-dimethylaminopyridine (lOOmg) and dichloromethane (lOOcm3) was treated with portions of dicyclohexyl '`31. ~ L~ 7 carbodiimide (2.~g) at the ambient temperature (ca. 24C).
After stirring for two hours the mixture was kept at the ambient temperature for 1~ hours, filtered and the collected solids washe,d with dichloromethane. ~he combined filtrate and washings were concentrated by evaporation of the solvent under reduced pressure and the residual oil purified by h.p.l.c. (Gilson) using a silica column eluted with a mixture of dichloromethane (100 parts by volume) and ethyl acetate (5 parts by volume). The initial fractions yielded a mixture of the ~esired product with 3-phenoxybenzalaehyde, the later fractions gave pure (+) ~-cyano-3-phenoxybenzyl (~)-trans-3-[2-(2-methylprop-2-yl) pyrimidin-5-yl]-2/2-dimethylcyclopropane carboxylate (5.3g) in the form of a gum consistin~ of a mixture of two racemic pairs of enantiomeri.c isomers in a ratio of 2~ he initial fractions were rechromatographe~ using a 2.5cm silica column and the ~ame eluent at a rate of 30cm3/minute to give the faster running (less polar) pair of enantiomeric isomers (120mg). The more polar (aster running) pair of enantiomeric isomers (21mg) was obtained by similar rechromatography of the later ractions (containing the 2:1 mixture (A) of isomer pairs). The product consisted of a 95:5 mixture of the more polar and less polar isomers. Recombination of rejected ractions and evaporation ~ave a 7:1 mixture (B) of the less polar and more polar isomers.
In biolo~ical tests using adult red spider mites (Tetranychus urticae) on rench bean leaves the more polar pair of enantiomeric isomers was about ten times more effective (LC50=4.5ppm) than t'ne less polar pair (LC50=49ppm).
A mi~ture of the lsss polar and more polar pairs of enantiomeric isorners in a ratio of 7:1 (lOmg) was dissolved in isopropanol (O.lcm3) containing triethylamine (5~ by weiyht) was stirred at room temperature. After 22.5 hours the ratio was approximately 1:1 due to base induced epimerisation at the ~ carbon of the alcohol moiety.
H ~MR (CDC13) ~ o (A) 0.95 (s); 1.0 (s); 1-35 (s), 1.4 (s); 1.45 (s); 2.0 (2d);
S 2.6 (2d); 6.4 (2s); 7.2 (m); 8O45 (2s) (Integration consistent with 2:1 mixture of diastereoisomers).
(B) 1.0 (s,3H); 1.40 (s,9H); 1.45 (s,3H); 2.05 (d,lH); 2.55 (d,l~);
6.40 (s,lH); 7.2 (m,9EI); 8.40 (s,2H) Infra red (liquid film) : (A) 2960, 1740, 1590, 1490, 1445, 1250, 1140, 695 cm~
15 (B) 2960, 1740, 1585, 1480, 1445, 12~5, 1140, 695 cm~
EX~MPLE 13 Preparation of methyl (~)-trans-2,2-dimethyl-3-formyl cyclopropane carboxylate.
A mixture of methyl 2,2-dimethyl-3-(dimethoxymethyl)-20 cyclopropane carboxylate (95~ (T)-trans isomer: 40.0~), glacial acetic acid (120 cm3), acetone (160 cm3~ and water (280 cm3) was stirred at the ambient temperature for 5 hours, diluted with water (1500 cm3) and extracted with diethyl ether (1000 cm3). The aqueous residue was washed 25 with ether (2 x 500 cm3) and the washings and ex.racis washed with saturated sodium bicarbonate solution untll free of acidity. After drying tha ethereal solution over anhydrous magnesium sulphate the solvent was removed by evaporation to yield a residual oil which was purified by distillation and methyl ~ trans-2,2-dimethyl-3-formylcyclopropane carboxylate (28.5 g~ collected as the fraction boiling at 46-48C/).05 mm HgO
Preparation of (+)-trans methyl 3-[(E,Z)-2-methoxy-vinyl~-2~dimethylcyclopropane carboxylate.
Sodium hydride (obtained by washing a 50% oil dispersion (9D6 g) with n-hexane to remove the oil) was suspended in dry dimethylsulphoxide (150 cm3, freshly distilled from calcium hydride) and the suspension stirred under a dry nitrogen atmosphere at 3~-40C for 5 hours. A
solution o~ methoxymethyl triphenyl phosphonium chloricle ( 68 ~ 8 g) in dry dimethylsulphoxide (200 cm3) was added over 15 minutes whilst the reaction temperature was maintained at ca. 20C by external cooling. The solution o~ the ylid thus produced was added dropwise to a stirred solution of methyl (+)-trans-2,2-dimethyl-3-formylcyclopropane carboxylate (28.5 g, ~reshLy distilled) in 2~ dimethylsulphoxide (50 cm3) whilst keeping the reaction temperature ~t ca. 20C over a period of 2 hours. The mixture was stirred for a further 30 minutes and then Xept at the ambient temperature for 72 hours. r1ater (1500 cm3) was added, and the mixture extracted with diethyl ether 25 (1 x 1000 cm3), 2 x 500 cm3). The extracts were combined, washed with water (3 x 300 cm3) and dried over anhydrous magnesium sulphate. The solvent was remov~d by evaporation under reduced pressure ancl the residue triturated with petroleum ether (boiling range 60-80C, 150 cm3). The undissolved solid was removed by filtration and the filtrate evaporated to give a yellow oil (29.0 g) which was distilled under reduced pressure using a Kugelrohr apparatus to yield methyl t+)-trans-3-~(E,Z)-2-methoxy-vinyl]-2,2-dirtethylcyclopropane carboxylate (21.4 g), boiling point 64C/O.OS mm E~g.
lH NMR (CDC13) ~ : 1.13 (s); 1.24 (s); 1.26 ~s); 1.4 (m);
1.9 (m); 203 (m); 3.5 (s); 3.6 (s);
3066 (s); 401 (2d); 4.56 (2d); 600 (dd), 6.4 (d).
(Integration consistent with 2:1 mixture of (E) and (Z) isomers~.
10 Infra red (liquid film) : 2960, 1730, 1650, 14~0, 1270, 1235, 1170, 920 c~-l.
EXAMPL~ 15 This example illustrates the preparation of a mixture o methyl (~)-trans-3-[(E,Z)-2-dimethylamino-1-formyl-__ vinyl]-2,2-dimethylcyclopropane carboxylate and methyl (~)-trans-3-~(E,Z)-formyl-2-methoxyvinyl~-2,2-dimethylcyclo--propane carboxylate.
A solution of phosphoryl chloride (12.0 cm3) in 1,2-dichloroethane (10.0 cm3) was added dropwise to a stirred mixture of dimethylformamide (29.5 cm3) and 1,2-dichloroethane (100 cm3) at the ambient temperature.
When the addition was complete the mixture was stirred for a further 15 minutes and cooled to 15~C. To this mixture was added portionwise a solution of methyl (+)-trans-3-~(~,Z)-2-methoxyvinyl~-2,2-dimethylcyclopropane carboxylate (10.0 g) in 1,2-dichloroethane (80 cm3). The mixture was kept at the ambient temperature for 16 hours and solid anhydrous potassium carbonate (150 g) and ice added. ~nen the exothermic reaction had subsided the mixture was extracted with methylene chloride (2 x 300 cm3) and extracts combined and wa~hed with water (300 cm3). After drying over anhydrous magnesium sulphate the solvent was removed by evaporation under reduced pressure and the residual oil heated at 55C and 0.05 mm Hg in a Kugelrohr apparatus to remove the volatile components to yield a mixture containiny a minor amount of methyl (+)-trans 3-L(E,Z)-l-formyl-2-methoxy-vinyll-2,2-dimethylcyclopropane carboxylate and a major amount of methyl (+)-trans-3-~(E,Z)-l-dimethylamino-l-formylvinyl]-2,2-dimethyl-cyclopropane carboxylate (A), (10.3 g).
lH ~MR (CDC13) ~ : (A) 1.0 (s); 1.05 (s); 1~27 (s); 1030 (s); 2.0 (m); 3.18 (s); 3.37 (s), 3.68 (s); 3.70 (s); $.75 (broad 5);
8.35 (broad s); 8.8 (s) (Integration consistent with 2:1 mixture of (E) and (Z) isomers).
Infra red (paraEfin mull) : 29G0, 2720, 1730, 1600, 1450, 1410, 12~0, 1230, 1175 cm~
This Example illustrates the preparation of methyl -(+)-trans-3-(2-cyclohexylpyrimidin-5-yl)cyclopropane carboxylate.
Sodium methoxide (3.2 cm3 of a 2M solution in methanol) was added dropwise to a stirred mixture of methyl (~)-trans-3-L(E,Z)-2--dimethylamino 1-formylvinyl~-2,2--dimethylcyclopropane carboxylate tl.0 g, in the form OL the product of Example 15 containing a minor propor~ion of methyl (+)-trans-3-[E,Z-l-formyl-2-methoxyvinyl]-2,2-dime-thylcyclopropane carboxylate), cyclohexanoyl amidine (1.08 g) and methanol (8 cm3) at the ambient temperature and the resultant mixture heated at the reflux temperature for 3.5 hours. The mixture was cooled to the ambient temperature and poured into water (200 cm3) and extracted with diethyl ether (2 x 200 cm3). After washing the combined extracts with water (50 cm3) and drying over anhydrous magnesium sulphate, the solvent was removed by evaporation under reduced pressure the residual oil was purified by column chromatoyraphy using silica column eluted with a mixture of methylene chloride (3 parts by volume) an diethyl ether (1 part by volume) to yield methyl (+)-trans-3-[(~,Z)-2 dimethylamino-1-formylvinyl]-2,2-dimethylcyclopropane carboxylate (790 mg).
MR (CDC13) ~ : 1.0 (s,3H); 1.4 (s,3H); 1.2-1.3 (b,lOH);
1.95 (d,lH); 2.5 (d,lH); 2.8 (b,lH);
3.7 (s,3H), 8.5 (s,2H).
Infra red (liquid im): 2940, 2860, 1730, 1600, 1500, 1440, 1290, 1175 cm~l.
EXA~IPLE 17 The product of Example 16 (790 mg) was converted to (+)-trans-3-(2-cyclohexylpyrimidin-5-yl)-2,2-dimethyl-cyclopropane c~rboxylic acid (750 mg, m.p. 128-130C) by the use of a procedure similar to that described in Example 7 except that methanol was used in place of ethanol.
Infra red (paraffin mull): 3500-2200 (broad), l710, 1550, 1340, 1290, 1260, 1190, 1120 Mass spectroscopy (M~) : 274.
- 3~ -EXA~PLE 18 This Example illustrates the preparation of (RS)-1-cyano-1-(6-phenoxypyr ia- 2-yl)methyl (lRS, trans)~3~(2 cyclohexylpyrimidin-5-yl)-2,2 dimethylcyclopropane carboxylate.
Dicyclohexylcarbodimide (118 mg) was added to a stirred mixture of (~)-trans-3-(2-cyclohexylpyrimidin-5-yl)-2,2-dimethylcyclopropane carboxylate (150 mg), l-cyano-1-(6-phenoxypyrid-2 yl)methanol (130 mg), 4-dimethylaminopyridine (5 mg) and dichloromethane (5 cm3) and the mixture stirred at the ambient temperature or 7 hours, and kept for a further 16 hours without stirring.
The product was isolated by filtering through a silica column, eluting first with dichloromethane and then with a mixture of dichloromethane (20 parts by volume) and ethyl lS acetate (1 part by volume) to yield (RS)-l-cyano-1-(6-phenoxypyrid-2-yl)methyl (lRS, trans)-3-(2-cyclohexylpyrimidine-5-yl)-2,2-dimethylcyclopropane carboxylate, (248 mg) identified by n.m.r. as a 1:1 mixture o the two pairs of enantiomeric diastereomers.
20 lH ~MR (CDC13) ~ 0 (2s); 1.35 (s); 1.43 (s); 1.2-2.0 (bm); ? . 05 (m); 2.6 (m); 2.a5 (m);
6.35 (bs); 6.9 (d); 7.25 (m); 7.8 (dd);
~.45 (2s).
(Integration consistent with 1:1 mixture of diastereomers).
Infra red (liquid film~: 2940, 2860, 1745, 1600, 1450, 1150, 810, 70G cm~l.
By the use o~ procedures similar to that described in Example 16, the following compounds were also prepared from the relevant amidines.
(i) Methyl (~)-trans-3-(2-prop-2 ylpyrimidin-5-yl)-2,2-dimethylcyclopropane carboxylate.
H NMR (CDC13) ~ ~ 0.98 (s,3H), 1.30 (s,3H); 1.38 (s,3H~:
1.40 (s,3H); 1.95 (d,lH); 2.25 (d,lH);
3.2 (m,l~); 3.75 (s,lH); 8.48 (s,2H);
Infra red (liquid film): 2980, 1735, 1595, 1550, 1440, 1340, 1260, 1175, 830 cm~l.
(ii) ~lethyl (+)-trans-3-(2-cyclopropylpyrimidin-5-yl)-2,2-dimethylcyclopropane carboxylate.
H NMR (CDC13) ~ : 0.96 (s!3H); 1.05 (m,4H); 1.40 (s,3H);
1.95 (d,lH); 2.2 (m,lH); 2.5 (d,2H), lS 3.75 (9, 3H); 8.4 (s,2H).
In~ra red (liquid film) : 3010, 2960, 1730, 1600, 1550, 1470, 1445, 117S, 915 cm~l.
EXA~PLE 20 By the use o-f procedures similar to that described in Examples 17 and 18 the following insecticidal and acaricldal compound of formula I were obtained.
(i) 2-methyl~3-phenylbenzyl (+)-~rans-2,2-dimethyl-3-(2-prop-2-ylpyrimidin-5-yl)cyclopropane carboxylate.
H ~MR (CDC13) ~ : 0.99 (s,3H); 1.30 (s,3H); 1.38 (s,3H);
1.42 (s,3H); 2.1 (d,lH); 2025 (s,3H);
2065 (d,lH), 302 (m,lH); 5.27 (s,2H);
7.3 (m,8H); 8.49 (s~2H)o Infra red (liquid film): 2980, 1730, 1595, 15S0, 1425, 1240, 1165, 740, 710 c~-l (ii) (+)-l-cyano-1-(6-phenoxypyrid-2-yl)methyl (+)-trans-2,2-dimethyl-3-~2-prop-2-ylpyrimidin-5-yl)cyclo-propane carboxylateO
lH ~MR (CDC13) ~ : 1.00 (s); 1.03 (s); 1.31 (s); 1.36 (s);
1.38 (s); 1.42 (s); 2.05 (m); 2.60 (m), 3.2 (m); 6.35 (bs); 6.9 (d), 7.3 (m);
7.S (dd); 8~5 (2s).
(Integration consistent wi-th 1:1 mixture of diastereiqomers).
Infra red (liquid ~ilm) : 2980, 1745, 1595, 1580, 1450, 1280, 1150, 745, 700 cm~l.
(iii) (+)-l-cyano-l (6-phenoxypyrid-2-yl)methyl (+)-trans- 2,2-dimethyl-3-(2-cyclopropyl-pyrimidin-5-yl)cyclopropane carboxylate.
H NMR (CDC13) ~ : 1.0 (s), 1.03 (m); 1.06 (s); 1.34 (s);
1.42 (s); 2.0 (2d); 2.2 (m); 28 (m);
6.4 (s); 6.9 (d); 7.3 (m); 7.8 (dd);
8.35 (2s).
(Integration consistent with 1:1 mixture of diastereoisomers).
Infra red (liquid film): 3010, 2940, 1750, 1500, 1450, 1260, 1150, 910, &00, 700 cm~
- 37 - ~ 7 The insecticidal activity of Compounds I to VII is set out in the following Table as a grading of A, B or C where A indicates that 80-100o mortality was observed, B
indicates that 50-79% mortality was observed and C
indicates that 0 49% mortality was observed. The tests were conducted by supporting the test species on a medium (eg. leaves of a suitable food plantr or ilter paper) and spraying the pests and medium (contact test - "CT" in the Table) or by spraying the medium before placing the pests thereon (residual test - "RT" in the Table). Assessment of mortality was made 72 hours after spraying except for houseflies (Musca domestica) where the assessment was made after 24 hours. In the test the compounds were used in the form of aqueous composition comprising 500 parts per million of the compound prepared by dissolving the compound in mixture of solvents consisting of 4 parts by volume by acetone and 1 part by volume of diacetone alcohol and diluting the solution with water containin~ 0.01% by weight of a wetting agent ("Lissapol" NX - "Lissapol" is a Registered ~rade Mark).
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t.q ~ ~ .~ ~ ~ .~N O ~1 ~d ~ H h ~ ~a -1 O l~ O 1~ O
E~ ~ u~ E~ J 11, ~ ~4 a ~0 ~, ~ ~ ~ ~ ~ ~ , ~ ~, ~_~?rJ ~
In the Table it can be seen that the compounds exhibit useful insecticidal and acaricidal activity against a number of test species representing a wide variet~ of insect and acarine pests of economic importance.
~DB/jlw 22 Feb 85
Infra red (paraEfin mull) : 29G0, 2720, 1730, 1600, 1450, 1410, 12~0, 1230, 1175 cm~
This Example illustrates the preparation of methyl -(+)-trans-3-(2-cyclohexylpyrimidin-5-yl)cyclopropane carboxylate.
Sodium methoxide (3.2 cm3 of a 2M solution in methanol) was added dropwise to a stirred mixture of methyl (~)-trans-3-L(E,Z)-2--dimethylamino 1-formylvinyl~-2,2--dimethylcyclopropane carboxylate tl.0 g, in the form OL the product of Example 15 containing a minor propor~ion of methyl (+)-trans-3-[E,Z-l-formyl-2-methoxyvinyl]-2,2-dime-thylcyclopropane carboxylate), cyclohexanoyl amidine (1.08 g) and methanol (8 cm3) at the ambient temperature and the resultant mixture heated at the reflux temperature for 3.5 hours. The mixture was cooled to the ambient temperature and poured into water (200 cm3) and extracted with diethyl ether (2 x 200 cm3). After washing the combined extracts with water (50 cm3) and drying over anhydrous magnesium sulphate, the solvent was removed by evaporation under reduced pressure the residual oil was purified by column chromatoyraphy using silica column eluted with a mixture of methylene chloride (3 parts by volume) an diethyl ether (1 part by volume) to yield methyl (+)-trans-3-[(~,Z)-2 dimethylamino-1-formylvinyl]-2,2-dimethylcyclopropane carboxylate (790 mg).
MR (CDC13) ~ : 1.0 (s,3H); 1.4 (s,3H); 1.2-1.3 (b,lOH);
1.95 (d,lH); 2.5 (d,lH); 2.8 (b,lH);
3.7 (s,3H), 8.5 (s,2H).
Infra red (liquid im): 2940, 2860, 1730, 1600, 1500, 1440, 1290, 1175 cm~l.
EXA~IPLE 17 The product of Example 16 (790 mg) was converted to (+)-trans-3-(2-cyclohexylpyrimidin-5-yl)-2,2-dimethyl-cyclopropane c~rboxylic acid (750 mg, m.p. 128-130C) by the use of a procedure similar to that described in Example 7 except that methanol was used in place of ethanol.
Infra red (paraffin mull): 3500-2200 (broad), l710, 1550, 1340, 1290, 1260, 1190, 1120 Mass spectroscopy (M~) : 274.
- 3~ -EXA~PLE 18 This Example illustrates the preparation of (RS)-1-cyano-1-(6-phenoxypyr ia- 2-yl)methyl (lRS, trans)~3~(2 cyclohexylpyrimidin-5-yl)-2,2 dimethylcyclopropane carboxylate.
Dicyclohexylcarbodimide (118 mg) was added to a stirred mixture of (~)-trans-3-(2-cyclohexylpyrimidin-5-yl)-2,2-dimethylcyclopropane carboxylate (150 mg), l-cyano-1-(6-phenoxypyrid-2 yl)methanol (130 mg), 4-dimethylaminopyridine (5 mg) and dichloromethane (5 cm3) and the mixture stirred at the ambient temperature or 7 hours, and kept for a further 16 hours without stirring.
The product was isolated by filtering through a silica column, eluting first with dichloromethane and then with a mixture of dichloromethane (20 parts by volume) and ethyl lS acetate (1 part by volume) to yield (RS)-l-cyano-1-(6-phenoxypyrid-2-yl)methyl (lRS, trans)-3-(2-cyclohexylpyrimidine-5-yl)-2,2-dimethylcyclopropane carboxylate, (248 mg) identified by n.m.r. as a 1:1 mixture o the two pairs of enantiomeric diastereomers.
20 lH ~MR (CDC13) ~ 0 (2s); 1.35 (s); 1.43 (s); 1.2-2.0 (bm); ? . 05 (m); 2.6 (m); 2.a5 (m);
6.35 (bs); 6.9 (d); 7.25 (m); 7.8 (dd);
~.45 (2s).
(Integration consistent with 1:1 mixture of diastereomers).
Infra red (liquid film~: 2940, 2860, 1745, 1600, 1450, 1150, 810, 70G cm~l.
By the use o~ procedures similar to that described in Example 16, the following compounds were also prepared from the relevant amidines.
(i) Methyl (~)-trans-3-(2-prop-2 ylpyrimidin-5-yl)-2,2-dimethylcyclopropane carboxylate.
H NMR (CDC13) ~ ~ 0.98 (s,3H), 1.30 (s,3H); 1.38 (s,3H~:
1.40 (s,3H); 1.95 (d,lH); 2.25 (d,lH);
3.2 (m,l~); 3.75 (s,lH); 8.48 (s,2H);
Infra red (liquid film): 2980, 1735, 1595, 1550, 1440, 1340, 1260, 1175, 830 cm~l.
(ii) ~lethyl (+)-trans-3-(2-cyclopropylpyrimidin-5-yl)-2,2-dimethylcyclopropane carboxylate.
H NMR (CDC13) ~ : 0.96 (s!3H); 1.05 (m,4H); 1.40 (s,3H);
1.95 (d,lH); 2.2 (m,lH); 2.5 (d,2H), lS 3.75 (9, 3H); 8.4 (s,2H).
In~ra red (liquid film) : 3010, 2960, 1730, 1600, 1550, 1470, 1445, 117S, 915 cm~l.
EXA~PLE 20 By the use o-f procedures similar to that described in Examples 17 and 18 the following insecticidal and acaricldal compound of formula I were obtained.
(i) 2-methyl~3-phenylbenzyl (+)-~rans-2,2-dimethyl-3-(2-prop-2-ylpyrimidin-5-yl)cyclopropane carboxylate.
H ~MR (CDC13) ~ : 0.99 (s,3H); 1.30 (s,3H); 1.38 (s,3H);
1.42 (s,3H); 2.1 (d,lH); 2025 (s,3H);
2065 (d,lH), 302 (m,lH); 5.27 (s,2H);
7.3 (m,8H); 8.49 (s~2H)o Infra red (liquid film): 2980, 1730, 1595, 15S0, 1425, 1240, 1165, 740, 710 c~-l (ii) (+)-l-cyano-1-(6-phenoxypyrid-2-yl)methyl (+)-trans-2,2-dimethyl-3-~2-prop-2-ylpyrimidin-5-yl)cyclo-propane carboxylateO
lH ~MR (CDC13) ~ : 1.00 (s); 1.03 (s); 1.31 (s); 1.36 (s);
1.38 (s); 1.42 (s); 2.05 (m); 2.60 (m), 3.2 (m); 6.35 (bs); 6.9 (d), 7.3 (m);
7.S (dd); 8~5 (2s).
(Integration consistent wi-th 1:1 mixture of diastereiqomers).
Infra red (liquid ~ilm) : 2980, 1745, 1595, 1580, 1450, 1280, 1150, 745, 700 cm~l.
(iii) (+)-l-cyano-l (6-phenoxypyrid-2-yl)methyl (+)-trans- 2,2-dimethyl-3-(2-cyclopropyl-pyrimidin-5-yl)cyclopropane carboxylate.
H NMR (CDC13) ~ : 1.0 (s), 1.03 (m); 1.06 (s); 1.34 (s);
1.42 (s); 2.0 (2d); 2.2 (m); 28 (m);
6.4 (s); 6.9 (d); 7.3 (m); 7.8 (dd);
8.35 (2s).
(Integration consistent with 1:1 mixture of diastereoisomers).
Infra red (liquid film): 3010, 2940, 1750, 1500, 1450, 1260, 1150, 910, &00, 700 cm~
- 37 - ~ 7 The insecticidal activity of Compounds I to VII is set out in the following Table as a grading of A, B or C where A indicates that 80-100o mortality was observed, B
indicates that 50-79% mortality was observed and C
indicates that 0 49% mortality was observed. The tests were conducted by supporting the test species on a medium (eg. leaves of a suitable food plantr or ilter paper) and spraying the pests and medium (contact test - "CT" in the Table) or by spraying the medium before placing the pests thereon (residual test - "RT" in the Table). Assessment of mortality was made 72 hours after spraying except for houseflies (Musca domestica) where the assessment was made after 24 hours. In the test the compounds were used in the form of aqueous composition comprising 500 parts per million of the compound prepared by dissolving the compound in mixture of solvents consisting of 4 parts by volume by acetone and 1 part by volume of diacetone alcohol and diluting the solution with water containin~ 0.01% by weight of a wetting agent ("Lissapol" NX - "Lissapol" is a Registered ~rade Mark).
-38 - ~L2~ 7 _ H
, ~ ~ V O
.
Q
æ
H l¢ '¢ ~1 1¢ ~¢ ~¢ ~q 1¢
H
H
H ~ ¢ U
H l¢ ~e ~~C lCC C.) C) '3 r~
~E~
H .
a ~ ~ ~ ~ ~ o E~
~ r! In ,~
O ~ q O a) ~ a~ O O
1 4 1: P ~ au ~J ~ ~ N
~ O Id Q) ~ao a~
::~ ~ O o (hd C ~ aJ i!4 E~ 8 ~ h ~¢ ~ C h h h E~
~O~
, ~ ~ ~ tn ~ ~ .u .~ _ ~ ~ ~ 1 tq O ~ H ~ ~ ~ h u~
~ ~ a) ~ ~ ~ ~ a~ e ~ u~ ~ ~
H ~ h ~ ~ h ~ ~ h u~ rl (~ O _I (d C~
D~ :~ ~1 ~ O $~ ~ _ ,C ~ E~ ~ ~ Q 'a ~ ,_1 O
cq ~ ~ hC ~I h ,s: o Zq ~J O Sl O la 3 C) _I $.1 P h U ~ h U 0 O 0 N ~ O 0 O h ~ O U 0 O U
t~ ~1 ~ ,1~ ~ .~ N O rl ~ S~ H h ~ ~ _I O Lq O ~ O
~ O h ~2) ~ ~ ~ ~ ~: E O O ,1 ~ ~ h :5 ~ H U
E~ E~ ,~ ~ ::5 u~ ~: _ ~ _,~ ~ Q a ~ _ ~ _ ¢~ _ _ .
- 39 - g2~ 7 . _ _ V C~
X ~ I U
H
1_1 a x o ~ X
u x U ~ u ~ c~ o a:l ~
~ ~ U
~_ X ~ ~ U ~ C~ U ~ C) O E~ E~
H
~1 H h Ll ~3 ~ ~! a u~ a~ , j; ~ ~ o a) o O ~ 3 .
o u a\ ~ n o oo Q) O O
P~ 1~ ~ N ~ ~ IJ
a) 1~ o ~ rl ~ U _l :~ )~ o ~ d O
u~ ~,1 t!4,1 ~1 0 ~ U~l~ e u ..
~ ' t11 X h U~ ~
8 ~
, _ ~ ~ ~ .~ .~ _ U~ ~ U _ ~ ~ _ ~ ~
1~1 ~1 ~ ~ ~: $ Ei 1~ ~ ~
~U '~U -.~3 ,uc `-- ~ ~ h ~ ~q 1:~ ~A U ,a ~i ~ ,1 ~ ~
~ ~ ~ ~ ~~ ~ ,_ ~ ~ e ~ ~ o ~ ~ ~ o tO ~: 1~ Ll ~: 1~ ~U O N ~ O U 3 1~ 3 ~d O H ~
1~ h .~ ~ ~ ,~ ra3 1~ H ~ a) ,1 ~ rQ ~ O U ::1 ~ U
t.q ~ ~ .~ ~ ~ .~N O ~1 ~d ~ H h ~ ~a -1 O l~ O 1~ O
E~ ~ u~ E~ J 11, ~ ~4 a ~0 ~, ~ ~ ~ ~ ~ ~ , ~ ~, ~_~?rJ ~
In the Table it can be seen that the compounds exhibit useful insecticidal and acaricidal activity against a number of test species representing a wide variet~ of insect and acarine pests of economic importance.
~DB/jlw 22 Feb 85
Claims (10)
1. A compound of formula :
wherein R2 represents an ?-branched alkyl group containing from 3 to 6 carbon atoms, and R represents either (a) hydroxy, halo or alkoxy of up to six carbon atoms, or (b) the group -OR1 where R1 is the residue of an alcohol of formula R1OH which forms an insecticidal ester with chrysanthemic acid, permethrin acid or cyhalothrin acid.
wherein R2 represents an ?-branched alkyl group containing from 3 to 6 carbon atoms, and R represents either (a) hydroxy, halo or alkoxy of up to six carbon atoms, or (b) the group -OR1 where R1 is the residue of an alcohol of formula R1OH which forms an insecticidal ester with chrysanthemic acid, permethrin acid or cyhalothrin acid.
2. A compound according to claim 1 wherein R2 represents an ?-branched alkyl group containing from 3 to 6 carbon atoms and R represents a group of formula :
wherein X is oxygen, sulphur, vinylene or a group of formula -CR5=Y- where Y is nitrogen or CR5, R4 is hydrogen, methyl, cyano or ethynyl, each R5 is selected from hydrogen, halogen and alkyl of up to 4 carbon atoms optionally substituted with halogen, n is two, and R6 is hydrogen, halogen, alkyl of up to 4 carbon atoms, alkenyl of up to 6 carbonatoms, phenyl, phenoxy or benzyl, or phenyl, phenoxy or benzyl substituted with halogen or alkyl, provided that when R6 is hydrogen, halogen, alkyl or alkenyl, R4 may not represent methyl cyano or ethynyl.
wherein X is oxygen, sulphur, vinylene or a group of formula -CR5=Y- where Y is nitrogen or CR5, R4 is hydrogen, methyl, cyano or ethynyl, each R5 is selected from hydrogen, halogen and alkyl of up to 4 carbon atoms optionally substituted with halogen, n is two, and R6 is hydrogen, halogen, alkyl of up to 4 carbon atoms, alkenyl of up to 6 carbonatoms, phenyl, phenoxy or benzyl, or phenyl, phenoxy or benzyl substituted with halogen or alkyl, provided that when R6 is hydrogen, halogen, alkyl or alkenyl, R4 may not represent methyl cyano or ethynyl.
3. A compound according to claim 2 wherein R2 is selected from prop-2-yl, but-2-yl, pent-2-yl, pent-3-yl, 2-methylprop-2-yl, 2-methylbut-2-yl, cyclopropyl and cyclohexyl.
4. A compound according to claim 2 where R represents pentafluorobenzyloxy, 4-methyl-2,3,5,6-tetrafluoro-benzyloxy, 4-allyl-2,3,5,6-tetrafluorobenzyloxy, 4-methoxymethyl-2,3,5,6-tetrafluorobenzyloxy, 3-phenoxybenzyloxy, ?-cyano-3-phenoxybenzyloxy, 4-fluoro-3-phenoxybenzyloxy, ?-cyano-4-fluoro-3-phenoxybenzyloxy, ?-ethynyl-3-phenoxybenzyloxy, 2-methyl-3-phenylbenzyloxy, 6-phenoxypyrid-2-ylmethanol, 1-cyano-1-(6-phenoxypyrid-2-yl)methanol, or 1-(6-phenoxypyrid-2-yl)ethanol.
5. The compound ?-cyano-3-phenoxybenzyl trans-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl]-2,2-dimethylcyclo--propane carboxylate.
6. The compound of claim 5 in the form of the enantiomeric pair of isomers represented by (S)-?-cyano-3-phenoxybenzyl (1R,trans)-3-[2-(2-methyl-prop-2-yl)pyrimidin-5-yl]-2,2-dimethylcyclopropane carboxylate and (R)-?-cyano-3-phenoxybenzyl (1S,trans)-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl]-2,2-dimethylcyclopropane carboxylate.
7. The compound 1-cyano-1-(6-phenoxypyrid-2-yl)methyl trans-3-[2-(2-methylprop-2-yl)pyrimidin-5-yl]-2,2-dimethylcyclopropane carboxylate.
8. An insecticidal and acaricidal composition comprising as active ingredient a compound according to claim 1 wherein R represents a group OR1, in association with a diluent or carrier for the active ingredient.
9. A method of combating insect and acarine pests at a locus which comprises treating the locus with an insecticidally and acaricidally effective amount of the composition of claim 8.
10. A process for preparing a compound of claim 1 wherein either (a) an acid of formula II
where Q represents the hydroxy group and R2 has any of the meanings given hereinabove, may be reacted directly with an alcohol of formula R1-OH (III) where R1 has any of the meanings given in claim 1 the reaction taking place in the presence of an acid catalyst, or a dehydrating agent, or (b) an acid halide of formula II where Q represents a halogen atom, preferably a chlorine atom, and R2 has any of the meanings given in claim 1, may be reacted with an alcohol of formula III, the reaction taking place in the presence of a base, or (c) an acid of formula II where Q represents the hydroxy group or an alkali metal salt thereof, may be reacted with halide of formula Q1-R1 (IV) wherein Q1 represents a halogen atom, and R1 has any of the meanings given in claim 1 or with the quaternary ammonium salts derived from such halides with tertiary amines, or (d) a lower alkyl ester of formula (II) where Q
represents a lower alkoxy group containing up to six carbon atoms, and R2 has any of the meanings given in claim 1, is heated with an alcohol of formula III to effect a transesterification reaction.
where Q represents the hydroxy group and R2 has any of the meanings given hereinabove, may be reacted directly with an alcohol of formula R1-OH (III) where R1 has any of the meanings given in claim 1 the reaction taking place in the presence of an acid catalyst, or a dehydrating agent, or (b) an acid halide of formula II where Q represents a halogen atom, preferably a chlorine atom, and R2 has any of the meanings given in claim 1, may be reacted with an alcohol of formula III, the reaction taking place in the presence of a base, or (c) an acid of formula II where Q represents the hydroxy group or an alkali metal salt thereof, may be reacted with halide of formula Q1-R1 (IV) wherein Q1 represents a halogen atom, and R1 has any of the meanings given in claim 1 or with the quaternary ammonium salts derived from such halides with tertiary amines, or (d) a lower alkyl ester of formula (II) where Q
represents a lower alkoxy group containing up to six carbon atoms, and R2 has any of the meanings given in claim 1, is heated with an alcohol of formula III to effect a transesterification reaction.
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB848407810A GB8407810D0 (en) | 1984-03-26 | 1984-03-26 | Cyclopropane derivatives |
| GB8407810 | 1984-03-26 | ||
| GB848418612A GB8418612D0 (en) | 1984-07-20 | 1984-07-20 | Cyclopropane derivatives |
| GB8418612 | 1984-07-20 | ||
| GB8502778 | 1985-02-04 | ||
| GB858502778A GB8502778D0 (en) | 1985-02-04 | 1985-02-04 | Cyclopropane derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1247097A true CA1247097A (en) | 1988-12-20 |
Family
ID=27262308
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000477446A Expired CA1247097A (en) | 1984-03-26 | 1985-03-25 | Insecticidally active esters of pyrimidinylcyclopropanecarboxylic acids |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US4661488A (en) |
| EP (1) | EP0162538A3 (en) |
| AU (1) | AU576352B2 (en) |
| CA (1) | CA1247097A (en) |
| ES (3) | ES8707202A1 (en) |
| GB (1) | GB2157288B (en) |
| NZ (1) | NZ211377A (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8714233D0 (en) * | 1987-06-17 | 1987-07-22 | Ici Plc | Pyrimidine derivatives |
| GB8531637D0 (en) * | 1985-12-23 | 1986-02-05 | Ici Plc | Pyrimidine derivatives |
| US4962109A (en) * | 1985-12-23 | 1990-10-09 | Imperial Chemical Industries Plc | Insecticidally and acaricidally active pyrimidine esters and intermediates therefor |
| GB8617649D0 (en) * | 1986-07-18 | 1986-08-28 | Ici Plc | Fluorobenzyl esters |
| DE3935277A1 (en) * | 1989-10-24 | 1991-05-02 | Hoechst Ag | SULPHONATED HETEROCYCLIC CARBOXAMIDES, METHOD FOR THE PRODUCTION THEREOF, THEIR SUBSTANCES AND THEIR USE AS HERBICIDES OR GROWTH REGULATORS |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3818009A (en) * | 1969-12-29 | 1974-06-18 | Lilly Co Eli | Alpha, alpha-disubstituted-5-pyrimidinemethanes |
| JPS5675461A (en) * | 1979-11-22 | 1981-06-22 | Mitsubishi Chem Ind Ltd | Cyclopropanecarboxylic ester |
| US4379930A (en) * | 1981-09-14 | 1983-04-12 | The Dow Chemical Company | Preparation of 2-t-butyl-5-hydroxypyrimidine |
| US4474958A (en) * | 1982-06-18 | 1984-10-02 | The Dow Chemical Company | 2-Alkyl-5-halopyrimidines |
| FR2533556A1 (en) * | 1982-09-29 | 1984-03-30 | Roussel Uclaf | CYCLOPROPANE CARBOXYLATES WITH ALLENIC STRUCTURE, PROCESS FOR THEIR PREPARATION AND COMPOSITIONS COMPRISING SAME |
| GB8531637D0 (en) * | 1985-12-23 | 1986-02-05 | Ici Plc | Pyrimidine derivatives |
-
1985
- 1985-03-05 GB GB08505681A patent/GB2157288B/en not_active Expired
- 1985-03-05 EP EP85301519A patent/EP0162538A3/en not_active Ceased
- 1985-03-11 NZ NZ211377A patent/NZ211377A/en unknown
- 1985-03-15 US US06/712,252 patent/US4661488A/en not_active Expired - Fee Related
- 1985-03-18 AU AU40067/85A patent/AU576352B2/en not_active Ceased
- 1985-03-25 CA CA000477446A patent/CA1247097A/en not_active Expired
- 1985-03-26 ES ES541594A patent/ES8707202A1/en not_active Expired
-
1986
- 1986-01-16 ES ES550950A patent/ES8706647A1/en not_active Expired
- 1986-01-16 ES ES550949A patent/ES8706646A1/en not_active Expired
- 1986-11-10 US US06/928,461 patent/US4760143A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ES550950A0 (en) | 1987-07-01 |
| NZ211377A (en) | 1988-01-08 |
| GB2157288A (en) | 1985-10-23 |
| ES8706647A1 (en) | 1987-07-01 |
| AU4006785A (en) | 1985-10-03 |
| EP0162538A3 (en) | 1986-10-29 |
| US4661488A (en) | 1987-04-28 |
| ES541594A0 (en) | 1987-07-16 |
| ES8706646A1 (en) | 1987-07-01 |
| ES8707202A1 (en) | 1987-07-16 |
| ES550949A0 (en) | 1987-07-01 |
| GB8505681D0 (en) | 1985-04-03 |
| AU576352B2 (en) | 1988-08-25 |
| EP0162538A2 (en) | 1985-11-27 |
| US4760143A (en) | 1988-07-26 |
| GB2157288B (en) | 1988-10-26 |
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